Thèses sur le sujet « Phagocytic cell »
Pour voir les autres types de publications sur ce sujet consultez le lien suivant : Phagocytic cell.
Créez une référence correcte selon les styles APA, MLA, Chicago, Harvard et plusieurs autres
Consultez les 50 meilleures thèses pour votre recherche sur le sujet « Phagocytic cell ».
À côté de chaque source dans la liste de références il y a un bouton « Ajouter à la bibliographie ». Cliquez sur ce bouton, et nous générerons automatiquement la référence bibliographique pour la source choisie selon votre style de citation préféré : APA, MLA, Harvard, Vancouver, Chicago, etc.
Vous pouvez aussi télécharger le texte intégral de la publication scolaire au format pdf et consulter son résumé en ligne lorsque ces informations sont inclues dans les métadonnées.
Parcourez les thèses sur diverses disciplines et organisez correctement votre bibliographie.
1
Chao, D. « The role of the accessory cell in the immune response ». Thesis, University of Oxford, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.382569.
Texte intégral
2
Pound, J. D. « Parameters of human macrophage activation ». Thesis, University of Nottingham, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.381442.
Texte intégral
3
Maslen, Christina Louise. « The effects of anti-inflammatory compounds on the oxidative metabolism of human phagocytic cells ». Thesis, University of Bath, 1985. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.353398.
Texte intégralRésumé :
Phagocytic cells respond to activation by a variety of stimuli by generating oxygen-derived free radicals. The characteristics of the production of superoxide anion and hydrogen peroxide by human neutrophils has been compared with that produced by human monocytes. The majority of work in this thesis is concerned with the employment of an assay which measures hydrogen peroxide produced by stimulated human neutrophils in vitro, but which also has been found to detect the generation of another peroxide, the identity of which is uncertain. The use of cyclooxygenase, lipoxygenase and phospholipase A2 pathway inhibitors has provided indirect evidence for the identification of the unknown peroxide as 5-hydroperoxyeicosatetraenoic acid (5-HPETE). These inhibitors have also provided the opportunity to investigate differences in the oxidative metabolism of human neutrophils induced by various stimuli. In addition, the effects of two cyclooxygenase inhibitors, diclofenac and piroxicam, on neutrophil activity in vivo has been investigated. Whilst neutrophil activity of some individuals was inhibited, this was not consistent and not significant. Incubation of a variety of analogues of the cyclooxygenase inhibitors diclofenac and fenclofenac with stimulated neutrophils in vitro has allowed an insight into the structure-activity relationships of these drugs' effects on neutrophil activity. It was found that the position of substitution of various groups in the ring structure remote from the acid group had the biggest single influence on activity. Finally, the oxidative metabolism of neutrophils from patients with progressive systemic sclerosis, rheumatoid arthritis and peripheral vascular disease has been compared with that of neutrophils from healthy controls. The neutrophils from the progressive systemic sclerosis group were found to have increased activity both ex vivo and following incubation with heat-aggregated IgG. This has been shown to be associated with enhanced expression of Fc receptors on these cells.
4
Uszak-Woronowicz, Alicja. « Trypanosoma cruzi, study on parasite culture conditions and non-phagocytic host cell interaction ». Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp05/MQ63381.pdf.
Texte intégral
5
Johnson, E. M. « In vitro effects of antifungal drugs on Candida albicans and phagocytic cell function ». Thesis, University of Bristol, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.375031.
Texte intégral
6
Gibson, Joanne. « Characterisation of the differential phagocytic, cytokine and T cell activation potentials of bone marrow derived dendritic cells in response to C.albincans cell wall glycosylation ». Thesis, University of Aberdeen, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.542629.
Texte intégralRésumé :
This thesis study investigated the involvement of glycosylation of cell wall proteins, major components of the outermost cell wall layer of C. albicans, in the induction of murine bone marrow derived dendritic cell (BMDC) responses. Utilising mutants which are deficient in glycosylation process, the binding of specific N-glycosylation moieties was demonstrated to be important in triggering phagocytosis while changes in O-glycosylation moieties altered the secretion of multiple pro-inflammatory chemokines and cytokines. Importantly, BMDC-O-glycosylation and/or BMDC-inner cell wall constituent interactions were demonstrated to result in the modulation of T cell responses, through the stimulation of the secretion of interleukin (IL)-17. It was further shown using receptor-deficient BMDC and receptor-blocking antibodies that although dectin-1, mannose receptor (MR) and Toll-like receptor (TLR)4 do not play a role in the induction of phagocytosis, receptor engagement induced receptor-specific cytokine secretion. Specifically, the secretion of IL-12p70 and IL-6 was dependent on dectin-1 signalling, while the secretion of the pro-inflammatory monocyte chemotactic protein (MCP)-1, tumour necrosis factor (TNF)-α and IL-6 were found to be induced in a MR-dependent manner. Intriguingly, a redundant role was found for TLR4. Cumulatively these results indicate a critical role of the recognition of fungal cell wall glycosylation moieties in the induction of protective phagocytosis and cytokine response in BMDC. Future studies to determine the role of other lectin receptors such as dectin-2 or receptor combinations will provide further insights into the complex interactions between BMDC and C. albicans.
7
Blomgran, Robert. « Microbe-induced apoptosis in phagocytic cells and its role in innate immunity ». Doctoral thesis, Linköping : Linköping University, 2006. http://www.bibl.liu.se/liupubl/disp/disp2006/med956s.pdf.
Texte intégral
8
Tolentino, Timothy P. « The Roles of Membrane Rafts in CD32A Mediated Formation of a Phagocytic Contact Area ». Diss., Georgia Institute of Technology, 2007. http://hdl.handle.net/1853/16127.
Texte intégralRésumé :
Membrane rafts are highly dynamic heterogeneous sterol- and sphingolipid-rich micro-domains on cell surfaces. They are generally believed to provide residency for cell surface molecules (e.g., adhesion and signaling molecules) and scaffolding to facilitate the functions of these molecules such as membrane trafficking, receptor transport, cell signaling, and endocytosis.
Using laser scanning confocal microscopy and reflection interference microscopy (RIM), we studied the spatial and temporal distributions of membrane rafts and surface receptors, signaling molecules, and cell organelles during the formation of phagocytic contact areas. K562 cells, which naturally express CD32A, a cell surface receptor for the Fc portion of Immuno-globulin g (IgG), was chosen as a model for neutrophils. An opsonized target was modeled using a glass supported lipid bilayer reconstituted with IgG. CD32A was found to cluster and co-localize with membrane rafts. Placing the K562 cells on the lipid bilayer triggered a process of contact area formation that includes binding between receptors and ligands, their recruitment to the contact area, a concurrent membrane raft movement to and concentration in the contact area, and transport of CD32A, IgG, and membrane rafts to the Golgi complex. Characterization of these processes was performed using agents known to disrupt detergent resistant membranes (DRMs), dissolve actin microfilaments, and inhibit myosin motor activity, which abolished the CD32A clusters and prevented the contact area formation.
The relevance to phagocytosis of contact area formation between K562 cells and lipid bilayers was demonstrated using micro-beads coated with a lipid bilayer reconstituted with IgG as the opsonized target instead of the glass supported planar lipid bilayer. Disruption of membrane rafts, salvation of the actin cytoskeleton, and inhibition of myosin II activity were found to inhibit phagocytosis.
Here we have provided evidence that membrane rafts serve as platforms that are used to pre-cluster CD32A and transport CD32A along the actin cytoskeleton to the site of phagocytic synapse formation, followed by internalization to the Golgi complex.
9
Phan, Toan Anh. « Ocular immunomodulating neuropeptides alpha-MSH and neuropeptide Y modulate phagocytic activity of the microphage cell line RAW 246.7 ». Thesis, Boston University, 2012. https://hdl.handle.net/2144/12591.
Texte intégralRésumé :
Thesis (M.A.)--Boston University
PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.The eye is an immune privileged tissue. Within the ocular microenvironment, there are regulatory mechanisms that suppress inflammation. These anti-inflammatory mechanisms are partly mediated by immunomodulating neuropeptides. We previously found that alpha-melanocyte stimulating hormone (α-MSH) and Neuropeptide Y (NPY) together induce activation of myeloid suppressor-like macrophages. In this study, we examined the possibility that α-MSH and NPY also modulate phagocytosis by macrophages. The monocytic cell line RAW 246.7 was treated with α-MSH and NPY at 1 ng/ml each, a concentration produced by retinal pigment epithelial cells in culture. The treated cells were fed florescent bioparticles of Gram(-) E. Coli or Gram(+) S. Aureus with or without opsin and assayed by flow cytometry. Also tested were the formation of phagolysosomes using pH sensitive florescent E. Coli or S. Aureus bioparticles with or without opsin, and the level of mannose receptors. The a MSH and NPY treated macrophages were significantly suppressed in their capacity to phagocytize unopsonized E. coli; however, suppression of S. Aureus phagocytosis was limited to NPY treated macrophages. In addition, α-MSH and NPY co-treatment suppressed phagocytosis and phagolysosome formation in the macrophages. Fluorescent microscopy imaging showed that there was a qualitative change in phagolysosome formation in opsonized bioparticle conjugates corresponding to the change seen in relative intensity measurements. There was no significant change in the number of man nose receptors in α-MSH, NPY, or α-MSH and NPY treated cells. As α-MSH and NPY together can induce suppressor macrophages within the ocular microenvironment, they can also modulate in a stimulus-dependent manner phagocytic signals within the macrophages. Therefore while the eye is protecting itself from the damaging effects of inflammation it may be making itself vulnerable by having less than optimal innate immune clearance of infectious pathogens.
10
Moghimi, S. Moein. « Tissue specific opsonins for phagocytic cells ». Thesis, Imperial College London, 1989. http://hdl.handle.net/10044/1/47572.
Texte intégral
11
Osman, Rim. « Etude de la calréticuline de la cellule en apoptose précoce et son interaction avec C1q et le phagocyte ». Thesis, Université Grenoble Alpes (ComUE), 2015. http://www.theses.fr/2015GREAV042/document.
Texte intégralRésumé :
L'efferocytose est un phénomène physiologique par lequel des millions de cellules apoptotiques sont efficacement éliminées par phagocytose sans provoquer une réaction inflammatoire. L'efficacité de ce processus nécessite une interaction rapide entre la cellule apoptotique et son phagocyte afin d'éviter l'entrée de la première dans une phase de nécrose secondaire. Cette interaction implique des motifs de la surface des 2 cellules qui peuvent interagir directement ou aussi indirectement via des molécules de pontage. Ce dernier rôle est associé à C1q, premier composant du système du complément. En effet, C1q favorise l'élimination des cellules apoptotiques et aussi la réponse tolérogène en interagissant avec des ligands présents de part et d'autre de la synapse efferocytaire. La calréticuline (CRT) de surface fait partie de ces ligands. Initialement connue comme co-récepteur, avec CD91, de la queue collagène de C1q à la surface du phagocyte, la CRT est aujourd'hui décrite comme un signal « eat-me » de la surface des cellules apoptotiques où elle peut aussi interagir avec les têtes globulaires de C1q. Des études récentes ont soulevé le potentiel immunogénique de la CRT, notamment au cours de la mort des cellules cancéreuses. Ainsi, la CRT de surface joue un rôle important dans l'efferocytose même si l'on ne sait pas exactement comment cette protéine chaperonne résidente du réticulum endoplasmique est exposée à la membrane plasmique. Dans un premier temps, j'ai démontré que la CRT augmente à la surface des cellules Jurkat rapidement après l'induction de l'apoptose, à un stade où la phosphatidylsérine, marqueur emblématique de l'apoptose, n'est pas encore détectée. D'une manière intéressante, C1q est capable d'interagir directement avec la CRT exposée à la surface des cellules à ce stade « pré-apoptotique », et de favoriser significativement leur phagocytose par les macrophages THP1. Dans un deuxième temps, j'ai mis en évidence la présence de la CRT dans le milieu extracellulaire et montré qu'elle varie avec l'évolution de l'apoptose. De plus, la CRT soluble est capable d'induire la migration des macrophages THP1, d'augmenter l'expression à leur surface de CD14, récepteur impliqué dans l'efferocytose, et de stimuler la macropinocytose, un processus utilisé par les phagocytes lors de la phagocytose des cellules apoptotiques. Cela suggère que la CRT extracellulaire peut moduler la biologie du phagocyte. Enfin, la CRT exogène peut se lier à la surface des macrophages et peut être ainsi une source externe de la CRT retrouvée à la surface des phagocytesEfferocytosis is a physiological phenomenon whereby millions of apoptotic cells are efficiently removed by phagocytosis without inducing an inflammatory response. The efficiency of this process requires rapid interaction between the apoptotic cell and the phagocyte in order to prevent the entry of the dying cell in a secondary necrosis phase. This interaction involves patterns of the surface of the 2 cells that can interact directly or indirectly via bridging molecules. The latter role is associated to C1q, the first component of the complement system. Indeed, C1q promotes the removal of apoptotic cells and the tolerogenic response by interacting with ligands present on either side of the efferocytic synapse. Surface exposed calreticulin (CRT) is one of these ligands. Initially known as the co-receptor, with CD91, to the collagenous tail of C1q on the phagocyte surface, CRT is now described as an “eat-me" signal of the apoptotic cell surface where it can also interact with the globular heads of C1q. Recent data have revealed the immunogenic potential of CRT, especially in the case of cancer cell death. Thus, surface exposed CRT plays an important role in efferocytosis even if it is not fully understood how this reticulum endoplasmic resident protein gets to the plasma membrane. I firstly demonstrated that CRT increases rapidly on the surface of Jurkat cells after the induction of apoptosis, at a stage where phosphatidylserine, emblematic marker of apoptosis, is not yet detected. Interestingly, C1q is capable of interacting directly with this “pre-apoptotic” cell surface exposed CRT, and promotes significantly the uptake of Jurkat cells by THP1 macrophages at this stage. Secondly, I demonstrated the presence of CRT in the extracellular medium whose content depends on the evolution of apoptosis. Furthermore, soluble CRT induces the migration of THP1 macrophages, increases their surface expression of CD14, a receptor involved in efferocytosis, and stimulates macropinocytosis, a process used by phagocytes during phagocytosis of apoptotic cells. These results suggest that the extracellular CRT can modulate the biology of the phagocyte. Finally, exogenous CRT binds to the surface of macrophages and can therefore be an external source of the CRT found on the phagocyte surface
12
Eriksson, Sofia. « Genetic adaptation of Salmonella enterica to phagocytic cells / ». Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-403-8/.
Texte intégral
13
O'Brien, David Kenneth. « The Interactions of Clostridium Perfringens With Phagocytic Cells ». Diss., Virginia Tech, 2003. http://hdl.handle.net/10919/27164.
Texte intégralRésumé :
Clostridium perfringens is the most common cause of gas gangrene (clostridial myonecrosis), a disease that begins when ischemic tissues become contaminated with C. perfringens. C. perfringens quickly multiplies in ischemic tissues and spreads to healthy areas, leading to high levels of morbidity and mortality. As a species, the bacterium can synthesize thirteen different toxins. The alpha toxin (PLC) and perfringolysin O (PFO) are thought to be important virulence factors in gangrene. We wished to understand how C. perfringens is capable of avoiding killing by the host immune system, and determine if PLC and PFO play a role in this avoidance. We found C. perfringens was not killed by J774-33 cells or mouse peritoneal macrophages under aerobic or anaerobic conditions. Using electron microscopy, we showed that C. perfringens could escape the phagosome of J774-33 and mouse peritoneal macrophages. We believe the ability of C. perfringens to survive in the presence of macrophages is due to its ability to escape the phagosome. Using a variety of inhibitors of specific receptors, we identified those used by J774-33 cells to phagocytose C. perfringens. The scavenger receptor, mannose receptor(s), and complement receptor (CR3) were involved in the phagocytosis of C. perfringens. To determine if PFO or PLC were involved in the ability of C. perfringens to survive in the presence of macrophages, we constructed C. perfringens strains lacking these toxins. The ability of C. perfringens to survive in the presence of J774-33 cells is dependent on PFO, while survival in mouse peritoneal macrophages is dependent on PFO and PLC. The ability of C. perfringens to escape the phagosome of J774-33 cells and mouse peritoneal macrophages is mediated by either PFO or PLC. Using a mouse model, we found that PFO and PLC were necessary for C. perfringens to survive in vivo using infectious doses 1000 times lower than those required to initiate a gangrene infection. We propose that PFO and PLC play a critical role in the survival of C. perfringens during the early stages of gangrene infections, when phagocytic cells are present and bacterial numbers are low.Ph. D.
14
Westermark, Linda. « Yersinia-phagocyte interactions during early infection ». Doctoral thesis, Umeå universitet, Institutionen för molekylärbiologi (Medicinska fakulteten), 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-79852.
Texte intégralRésumé :
Pathogenic Gram-negative Yersinia species preferentially target and inactivate phagocytic cells of the innate immune defense by translocation of effector Yersinia outer proteins (Yops) into the cells via a type III secretion system. This indicates that inactivation and avoidance of the early innate immune response is an efficient way for Yersinia species to avoid elimination and to cause diseases ranging from mild gastroenteritis (Y. pseudotuberculosis and Y. enterocolitica) to plague (Y. pestis). In this project, we aimed to study the interaction between enteropathogenic Y. pseudotuberculosis and phagocytic cells during early infection. In situ interaction studies on infected intestinal tissues showed that Y. pseudotuberculosis mainly interacts with dendritic cells (DCs) in lymphoid tissues of the intestine during initial infection. After massive recruitment of polymorphonuclear neutrophils (PMNs) to the infected tissues, wild-type (wt) bacteria also interacted with this phagocyte. In contrast to the wt, mutants lacking the anti-phagocytic effectors YopH and YopE are avirulent in mice and unable to spread systemically. Interestingly, our interaction assay showed that these mutants not only interacted with DCs, but also with PMNs during the initial stage of infection. Thus, indicating that Y. pseudotuberculosis can avoid interaction with PMNs during early infection and that this is Yop-dependent. In a phagocytosis assay Y. pseudotuberculosis was demonstrated to inhibit internalization by DCs in a YopE-dependent manner, while both YopH and YopE were shown to be involved in the blocking of phagocytosis by macrophages and PMNs. Thus, indicating that YopH has cell type-specific effects. To further investigate the role of DCs during initial stages of infection, a mouse DC depletion model (CD11c-DTRtg) was applied. However, the DTx-mediated depletion of DCs in CD11c-DTRtg mice induced neutrophilia and the model could not give a definite answer to whether DCs play an important role in either restricting or stimulating progression of Y. pseudotuberculosis infection. To investigate involvement of PMNs during early infection mice were injected with the depleting antibody α-Ly6G. In absence of PMNs wt, as well as yopH and yopE mutants became more virulent, which further supports the importance of these Yops for the ability of Y. pseudotuberculosis to disseminate from the initial infection sites in the intestine to cause systemic disease. In summary, our studies show that inhibiting internalization and maturation of DCs and avoiding phagocytosis by and interaction with macrophages and PMNs during the early stages of infection are important virulence strategies for Y. pseudotuberculosis to be able to colonize tissues, proliferate and disseminate systemically.
15
Murdoch, Craig. « Multi-spanning transmembrane receptors on endothelial and epithelial cells ». Thesis, University of Sheffield, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.310809.
Texte intégral
16
Sanchez, Yasmin. « Characterization, expression and resgulation of the ferric reductase Dcytb in phagocytic cells ». Thesis, King's College London (University of London), 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.440462.
Texte intégral
17
Waite, Alicia Achiaa Charlotte. « The crucial roles of mononuclear phagocytic cells during ventilator-induced lung injury ». Thesis, Imperial College London, 2012. http://hdl.handle.net/10044/1/14502.
Texte intégralRésumé :
Acute respiratory distress syndrome remains a significant cause of mortality among intensive care patients. Mechanical ventilation is a crucial component of therapy but can exacerbate injury through overstretch of lung units, known as ventilator-induced lung injury (VILI). The mechanisms by which ventilation triggers the characteristic inflammatory cascade and how this pulmonary inflammation progresses to extrapulmonary organs have not been clearly elucidated. In this work I explored the role of mononuclear phagocytes in the initiation (alveolar macrophages) and subsequent progression (monocytes) of VILI, using in vivo mouse models. Initially, the importance of alveolar macrophages in VILI was clarified by pharmacologically depleting these cells, which substantially attenuated injury. The observation that injurious ventilation led to a decrease in macrophage recoverability led us to hypothesise that adhesive interactions between epithelial cells and macrophages may be important in their activation. To address this, I developed a novel flow cytometric methodology to assess intracellular mitogen activated protein (MAP) kinase phosphorylation in discrete pulmonary cell populations. I was able to demonstrate rapid alveolar macrophage activation, but little epithelial activation, during high stretch ventilation. This potentially indicated that alveolar macrophages directly sense stretch through their adhesive contacts with epithelial cells. I attempted to study this using antibodies to block integrin-mediated interactions, although results were inconclusive. In addition to these experiments, I carried out a preliminary study showing, for the first time, that activated leukocytes marginate to extrapulmonary organs during VILI. This supports the possibility that monocytes and neutrophils play a role in the development of extra-pulmonary organ injury, although this remains undefined. This data shows that mononuclear phagocytic cells are likely to play crucial roles in the pathogenesis of VILI. The findings and methodologies developed provide many possibilities for future research that will enhance our understanding of this iatrogenic injury, ultimately in view of potential therapeutic targets.
18
Valério, Michele Janegitz Acorci [UNESP]. « Papel dos receptores Toll-Like na atividade dos neutrófilos humanos desafiados com a cepa de alta virulência do Paracoccidioides brasiliensis ». Universidade Estadual Paulista (UNESP), 2009. http://hdl.handle.net/11449/101476.
Texte intégralRésumé :
Made available in DSpace on 2014-06-11T19:31:28Z (GMT). No. of bitstreams: 0
Previous issue date: 2009-03-31Bitstream added on 2014-06-13T19:01:44Z : No. of bitstreams: 1
valerio_mja_dr_botfm.pdf: 1362288 bytes, checksum: 92bb90e388b3c540e45ec3f19d6b0e1d (MD5)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Universidade Estadual Paulista (UNESP)
Na paracoccidioidomicose, os estudos sobre os mecanismos de defesa do hospedeiro destacam o papel das células fagocitárias que participam ativamente dos mecanismos efetores diretos contra o fungo e da modulação da resposta inflamatória. Dentre essas células, nos últimos anos, os estudos têm se voltado para os neutrófilos, que exercem um importante papel efetor e modulador principalmente durante os estágios iniciais da infecção. As funções dessas células, incluindo as antimicrobicidas, podem ser reguladas por citocinas pró e anti-inflamatórias. Apesar dos mecanismos celulares e moleculares desse processo não estarem completamente entendidos, trabalhos nos últimos anos têm mostrado de forma bastante consistente o envolvimento dos “Toll Like Receptors” (TLRs). Neste contexto, os objetivos do presente trabalho foram: 1- Avaliar a expressão de TLR2 e TLR4 por neutrófilos humanos pré-ativados com GM-CSF, IL-15, TNF-a ou IFN-g e desafiados com cepa virulenta de Paracoccidioides brasiliensis cepa 18 (Pb18). 2- Avaliar a participação desses receptores na atividade fungicida, produção de H2O2 e das citocinas: IL-6, IL-8 e TNF-a e IL-10 por neutrófilos humanos pré-ativados com GM-CSF, IL-15, TNF-a, IFN-g e desafiados com Pb18. Nos ensaios referentes ao primeiro objetivo, as células foram tratadas por 18 horas com cada uma das citocinas ou LPS, posteriormente desafiadas com Pb 18 por 4 horas e avaliadas quanto a expressão de TLR2 e TLR4 por citometria de fluxo. Nos referentes ao segundo objetivo, as células foram ativadas com os mesmos estímulos, submetidas ao bloqueio de TLR2 e TLR4, através da incubação das células com anticorpos monoclonais específicos, desafiadas com Pb18 por 4 horas e analisadas quanto a atividade fungicida, produção de H2O2 e das citocinas IL-6, IL-8 e TNF-a e IL-10, por Elisa. Os resultados...
In paracoccidioidomycosis, phagocytic cells appear to provide one of the major lines of host defense. In this context, in last years, various studies have focused on the role of neutrophils that are involved in primary response to the fungus. Neutrophil functions are regulated by pro and anti-inflammatory cytokines. The molecular and cellular mechanisms involved in this process are not fully understood, but there are strong evidences about the involvement of “Toll Like Receptors” (TLRs). In this context, we aimed to evaluate TLR2 and TLR4 expression on human neutrophils primed with the cytokines GM-CSF, IL- 15, TNF-a or IFN-g and challenged with a virulent strain of Paracoccidioides brasiliensis (Pb18). Moreover, we asked if these receptors have a role on fungicidal activity, H2O2 and IL-6, IL-8, TNF-a and IL-10 production, by primed and challenged cells. In first assays, neutrophils were incubated with each of cytokines or LPS by 18 h, challenged with Pb18 by 4 h and evaluated by TLR2 and TLR4 expression by flow cytometry. In other assays, cells were incubated with each of cytokines or LPS by 18h, submitted to TLR2 and TLR4 blocking by specific monoclonal antibodies, challenged with Pb18 for 4 h and evaluated for fungicidal activity, H2O2 and IL-6, IL-8, TNF-a and IL-10 production, by ELISA. All cytokines increased TLR2 and TLR4 expression. Pb18 increased TLR2 expression inducing an additional effect to that of cytokines. On the contrary, it inhibited TLR4 expression. All cytokines increased neutrophils fungicidal activity, but this process was not associated with TLR2 or TLR4 expression. All cytokines and Pb18 increased H2O2 production, but in the same manner to fungicidal activity, the process was not associated to TLR2 or TLR4 expression. Neutrophils activation with GM-CSF and TNF-a resulted in a significative increase on IL-8... (Complete abstract click electronic access below)
19
Smith-Steinhart, Christine M. « TGF[beta] as a regulator of phagocytic competency in polarized mammary epithelial cells / ». Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2007.
Trouver le texte intégralRésumé :
Thesis (Ph.D. in Immunology) -- University of Colorado Denver, 2007.Typescript. Non-Latin script record Includes bibliographical references (181-196). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;
20
Shahraz, Anahita [Verfasser]. « Neuroprotective Effects of Polysialic Acid and SIGLEC-11 in Activated Phagocytic Cells / Anahita Shahraz ». Bonn : Universitäts- und Landesbibliothek Bonn, 2016. http://d-nb.info/1103024507/34.
Texte intégral
21
Valério, Michele Janegitz Acorci. « Papel dos receptores Toll-Like na atividade dos neutrófilos humanos desafiados com a cepa de alta virulência do Paracoccidioides brasiliensis / ». Botucatu : [s.n.], 2009. http://hdl.handle.net/11449/101476.
Texte intégralRésumé :
Resumo: Na paracoccidioidomicose, os estudos sobre os mecanismos de defesa do hospedeiro destacam o papel das células fagocitárias que participam ativamente dos mecanismos efetores diretos contra o fungo e da modulação da resposta inflamatória. Dentre essas células, nos últimos anos, os estudos têm se voltado para os neutrófilos, que exercem um importante papel efetor e modulador principalmente durante os estágios iniciais da infecção. As funções dessas células, incluindo as antimicrobicidas, podem ser reguladas por citocinas pró e anti-inflamatórias. Apesar dos mecanismos celulares e moleculares desse processo não estarem completamente entendidos, trabalhos nos últimos anos têm mostrado de forma bastante consistente o envolvimento dos "Toll Like Receptors" (TLRs). Neste contexto, os objetivos do presente trabalho foram: 1- Avaliar a expressão de TLR2 e TLR4 por neutrófilos humanos pré-ativados com GM-CSF, IL-15, TNF-a ou IFN-g e desafiados com cepa virulenta de Paracoccidioides brasiliensis cepa 18 (Pb18). 2- Avaliar a participação desses receptores na atividade fungicida, produção de H2O2 e das citocinas: IL-6, IL-8 e TNF-a e IL-10 por neutrófilos humanos pré-ativados com GM-CSF, IL-15, TNF-a, IFN-g e desafiados com Pb18. Nos ensaios referentes ao primeiro objetivo, as células foram tratadas por 18 horas com cada uma das citocinas ou LPS, posteriormente desafiadas com Pb 18 por 4 horas e avaliadas quanto a expressão de TLR2 e TLR4 por citometria de fluxo. Nos referentes ao segundo objetivo, as células foram ativadas com os mesmos estímulos, submetidas ao bloqueio de TLR2 e TLR4, através da incubação das células com anticorpos monoclonais específicos, desafiadas com Pb18 por 4 horas e analisadas quanto a atividade fungicida, produção de H2O2 e das citocinas IL-6, IL-8 e TNF-a e IL-10, por Elisa. Os resultados... (REsumo completo, clicar acesso eletrônico abaixo)Abstract: In paracoccidioidomycosis, phagocytic cells appear to provide one of the major lines of host defense. In this context, in last years, various studies have focused on the role of neutrophils that are involved in primary response to the fungus. Neutrophil functions are regulated by pro and anti-inflammatory cytokines. The molecular and cellular mechanisms involved in this process are not fully understood, but there are strong evidences about the involvement of "Toll Like Receptors" (TLRs). In this context, we aimed to evaluate TLR2 and TLR4 expression on human neutrophils primed with the cytokines GM-CSF, IL- 15, TNF-a or IFN-g and challenged with a virulent strain of Paracoccidioides brasiliensis (Pb18). Moreover, we asked if these receptors have a role on fungicidal activity, H2O2 and IL-6, IL-8, TNF-a and IL-10 production, by primed and challenged cells. In first assays, neutrophils were incubated with each of cytokines or LPS by 18 h, challenged with Pb18 by 4 h and evaluated by TLR2 and TLR4 expression by flow cytometry. In other assays, cells were incubated with each of cytokines or LPS by 18h, submitted to TLR2 and TLR4 blocking by specific monoclonal antibodies, challenged with Pb18 for 4 h and evaluated for fungicidal activity, H2O2 and IL-6, IL-8, TNF-a and IL-10 production, by ELISA. All cytokines increased TLR2 and TLR4 expression. Pb18 increased TLR2 expression inducing an additional effect to that of cytokines. On the contrary, it inhibited TLR4 expression. All cytokines increased neutrophils fungicidal activity, but this process was not associated with TLR2 or TLR4 expression. All cytokines and Pb18 increased H2O2 production, but in the same manner to fungicidal activity, the process was not associated to TLR2 or TLR4 expression. Neutrophils activation with GM-CSF and TNF-a resulted in a significative increase on IL-8... (Complete abstract click electronic access below)
Orientador: Ângela Maria Victoriano de Campos Soares
Coorientador: Luciene Alarcão Dias Melicio
Banca: José Maurício Sforci
Banca: Sueli Aparecida Calvi
Banca: Gil Bernardi
Banca: Wafa Hanna Koury Cabrera
Doutor
22
Baharlou, Heeva. « The role of Anogenital Mononuclear Phagocytes in HIV transmission ». Thesis, The University of Sydney, 2022. https://hdl.handle.net/2123/29580.
Texte intégralRésumé :
The focus of thesis is the study of the sexual transmission of HIV. We have used human anogenital tissues to evaluate the role of Mononuclear Phagocyte Subsets in mucosal HIV transmission. This thesis is comprised of three papers. In the first paper we describe a novel subset of epidermal dendritic cell in human anogenital tissues and we show it is a preferential target for HIV uptake, infection and transfer to CD4 T cells. In the second paper we develop an algorithm to remove autofluorescence from microscopy images of human tissue and show it is essential to enable accurate quantification of HIV localisation to target cells in situ. This facilitated the third paper - the development of a novel pipeline to quantify HIV localisation patterns in human colorectal tissue in situ. This paper used RNAscope to detect HIV, multiplex fluorescence microscopy and customised image processing algorithms to visualise the dynamics of HIV transmission in human colorectal tissue within 2 hours of exposure to HIV. We show conclusively that HIV is first enriched in mucosal DCs and submucosal macrophages, but not CD4 T cells, and that it is preferentially enriched in lymphoid aggregates. We also provide circumstantial evidence that lamina propria DCs traffic virus to the centre of lymphoid aggregates which themselves provide a conduit for HIV entry to the submucosal layer, where it associates with macrophages. Finally, we show that HIV mucosal entry induces its target cells to form clusters in which HIV+ DCs and macrophages transfer virus to and enhance infection of CD4 T cells, supported by ex vivo data. This paper provides the most comprehensive quantitative in situ overview of early HIV transmission events in human mucosal tissue to date. Together these papers describe new target cells involved in HIV transmission and provide insights into the actual events that occur in human colorectal tissue immediately following HIV exposure.
23
Schönheit, Jörg. « A phagocyte-specific Irf8 gene enhancer establishes early conventional dendritic cell commitment ». Phd thesis, Universität Potsdam, 2011. http://opus.kobv.de/ubp/volltexte/2011/5548/.
Texte intégralRésumé :
Haematopoietic development is a complex process that is strictly hierarchically organized. Here, the phagocyte lineages are a very heterogeneous cell compartment with specialized functions in innate immunity and induction of adaptive immune responses. Their generation from a common precursor must be tightly controlled. Interference within lineage formation programs for example by mutation or change in expression levels of transcription factors (TF) is causative to leukaemia. However, the molecular mechanisms driving specification into distinct phagocytes remain poorly understood. In the present study I identify the transcription factor Interferon Regulatory Factor 8 (IRF8) as the specification factor of dendritic cell (DC) commitment in early phagocyte precursors.
Employing an IRF8 reporter mouse, I showed the distinct Irf8 expression in haematopoietic lineage diversification and isolated a novel bone marrow resident progenitor which selectively differentiates into CD8α+ conventional dendritic cells (cDCs) in vivo. This progenitor strictly depends on Irf8 expression to properly establish its transcriptional DC program while suppressing a lineage-inappropriate neutrophile program.
Moreover, I demonstrated that Irf8 expression during this cDC commitment-step depends on a newly discovered myeloid-specific cis-enhancer which is controlled by the haematopoietic transcription factors PU.1 and RUNX1. Interference with their binding leads to abrogation of Irf8 expression, subsequently to disturbed cell fate decisions, demonstrating the importance of these factors for proper phagocyte cell development.
Collectively, these data delineate a transcriptional program establishing cDC fate choice with IRF8 in its center.Die Differenzierung von hämatopoietischen Zellen ist ein komplexer Prozess, der strikt hierarchisch organisiert ist. Dabei stellen die Phagozyten eine sehr heterogene Zellpopulation dar, mit hochspezialisierten Funktionen im angeborenen Immunsystem sowie während der Initialisierung der adaptiven Immunreaktion. Ihre Entwicklung, ausgehend von einer gemeinsamen Vorläuferzelle, unterliegt einer strikten Kontrolle. Die Beeinträchtigung dieser Linienentscheidungsprogramme, z.B. durch Mutationen oder Änderungen der Expressionslevel von Transkriptionsfaktoren kann Leukämie auslösen. Die molekularen Mechanismen, welche die linienspezifische Entwicklung steuern, sind allerdings noch nicht im Detail bekannt. In dieser Arbeit zeige ich den maßgeblichen Einfluss des Transkriptionsfaktors Interferon Regulierender Faktor 8 (IRF8) auf die Entwicklung von dendritischen Zellen (DC) innerhalb der Phagozyten. Mittels einer IRF8-Reporter Maus stellte ich die sehr differenziellen Expressionsmuster von Irf8 in der hämatopoietischen Entwicklung dar. Dabei konnte ich eine neue, im Knochenmark lokalisierte, Vorläuferpopulation isolieren, die in vivo spezifisch Differenzierung in CD8α+ konventionelle dendritische Zellen (cDC) steuert. Dieser Vorläufer ist dabei absolut von der Expression von Irf8 abhängig und etabliert auf transkriptioneller Ebene die dendritische Zellentwicklung, während gleichzeitig die Entwicklung neutrophiler Zellen unterdrückt wird. Darüber hinaus zeigte ich, dass Irf8 Expression während der cDC Entwicklung von einem neu charakterisierten cis-regulatorischen Enhancer abhängt, der spezifisch in myeloiden Zellen agiert. Ich konnte zeigen, dass die hämatopoietischen Transkriptionfaktoren PU.1 und RUNX1 mittels dieses Enhancers die Irf8 Expression steuern. Können diese beiden Faktoren nicht mit dem Enhancer interagieren, führt das zu stark verminderter Irf8 Expression, damit zu Veränderungen in den Differnzierungsprogrammen der Zellen, was die Bedeutung dieses regulatorischen Mechanismus unterstreicht. Zusammengefasst beschreiben diese Daten die Etablierung der frühen cDC Entwicklung, in der IRF8 die zentrale Rolle spielt.
24
Zhou, Cheng. « Enhanced phagocytic capacity endows chondrogenic progenitor cells with a novel scavenger function within injured cartilage ». Diss., University of Iowa, 2016. https://ir.uiowa.edu/etd/2307.
Texte intégralRésumé :
Articular cartilage underwent serious joint injuries seldom repair spontaneously and might progress to post-traumatic osteoarthritis. This is majorly because articular cartilage’s unique properties that lack blood and nerve supply intrinsically. This peculiar structure, in addition, generates an unfavorable environment for certain phagocytes (macrophages, monocytes, neutrophils, etc) to infiltrate to cartilage to scavenge debris from cartilage matrix and cell caused from joint injuries. Therefore, physiological and functional regeneration of damaged cartilage is urgently needed and several clinical techniques have been developed, including microfracture, autograft transplantation, autologous chondrocytes implantation.
We previously identified highly migratory cells emerged and repopulated in cartilage damaged surface after ~10 days of artificial cartilage injury. These cells were later named chondrogenic progenitor cells (CPCs) due to their enhanced potential of chondrogenic differentiation. However, this important finding contrasts the conventional theory that cartilage harbors only one cell type, chondrocytes. Here we hypothesize that CPCs are a distinct cell type in cartilage, and more importantly, one of CPCs’ crucial natures is to phagocytose debris more effectively than chondrocytes.
To test these, we first harvested CPCs from cartilage surfaces, chondrocytes, synovial cells (synoviocytes and synovial fluid cells) for microarray assay to evaluate the closeness among these joint cells on whole gene expression level. Quantitative PCR were then conducted to verify gene expression of certain functional interests. Moreover, debris from cell and extracellular matrix were generated and incubated with CPCs and chondrocytes to compare their phagocytic capacity via multiple experimental assessments.
In confocal microscopy examination, the emergence of CPCs could be clearly observed after cartilage injury. Aside from their distinguishable morphology compared to chondrocyte, CPCs possess several vital properties including highly migratory, chemotactic, clonogenic. Microarray data revealed that CPCs, from gene expression profile, are distinctively isolated from chondrocytes and are more akin to synovial cells. Additionally, the series of phagocytosis related experiments showed that CPCs are dramatically superior to chondrocytes in engulfing debris, along with enhanced lysosomal activities indicating the following debris degradation.
Taken all these data together, CPCs, activated by cartilage injury, emerged and migrated to damaged sites. They are a distinct cell type residing in cartilage apart from chondrocytes. Their enhanced capacity to sustainably phagocytose and clear debris provides a novel insight for cartilage regeneration and prevention of osteoarthritis.
25
Liu, Yuqing. « Effect of glucocorticoids on uptake of apoptotic cells by phagocytes ». Thesis, University of Nottingham, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.285768.
Texte intégral
26
Stonehouse, Timothy James. « Analysis of the role of RXR in monocyte-macrophage differentiation and function using U937 monoblastoid cells ». Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.321988.
Texte intégral
27
Shingler, William Heth. « Role of ICAM-3 in recognition of apoptotic cells by phagocytes ». Thesis, University of Nottingham, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.402935.
Texte intégral
28
Karimi, Gilda. « Etude de l'assemblage de la NADPH oxydase du phagocyte ». Thesis, Paris 11, 2014. http://www.theses.fr/2014PA112025.
Texte intégralRésumé :
La NADPH oxydase du phagocyte est une enzyme impliquée dans la défense immunitaire contre les pathogènes. Après activation du phagocyte, cette enzyme produit des ions superoxyde par réduction du dioxygène par le NADPH. Elle est constituée de quatre sous- unités cytosolubles (p47phox ; p67phox ; p40phox et Rac), et deux membranaires (gp91 ; p22phox). Son activation fait intervenir un processus complexe qui met en jeu des changements d’interaction entre les protéines la constituant et qui permet l’assemblage des six sous- unités. Afin d’obtenir des informations sur les processus d’assemblage et d’activation, j’ai reconstitué le complexe dans un système cell free à l’aide de protéines recombinantes pour pouvoir contrôler tous les paramètres. Dans ce travail nous avons comparé les modes d’activation de p47phox par phosphorylation, par mutation substitutionelle sérine - aspartate en position S303,S304 et S328 pour mimer la phosphorylation et enfin par addition d’acide arachidonique (AA) activateur connu de l’enzyme in vitro mais aussi in vivo. Bien qu’il ai été montré que ces trois méthodes ouvrent la protéine vers une conformation ayant des propriétés similaires, nous avons trouvé que les effets de ces méthodes d’activation sont significativement différents. Ainsi, les changement de conformation observés par dichroisme circulaire, sont dissemblables. Pour p47phox, l’addition de AA déstructure la protéine. La phosphorylation induit un déplacement bathochrome des bandes de CD qualitativement similaire, alors que les mutations S-D de p47phox provoquent un déplacement opposé. Pour le complexe p47phox-p67phox l’addition d’AA destructure le mélange tandis que la mutation induit relativement peu de changement. Nous avons mesuré les constantes de dissociation Kd du complexe p47phox-p67phox. Alors que pour les protéines « sauvages », le Kd est faible (4±2 nM), les mutations de p47phox ainsi que l’addition d’AA augmentent cette valeur jusqu’à environ 50 nM, montrant une diminution de l’affinité entre p47phox-p67phox. De même, sur le complexe entier, l’effet de la phosphorylation de p47phox est différent de la mutation. Nous avons mesuré les valeurs de EC50 relatives à p67phox pour les différentes formes de p47phox. L’activation de p47phox par phosphorylation diminue l’EC₅₀, alors que les doubles ou triple mutations augmentent sa valeur. Nous avons confirmé que la phosphorylation et la mutation sont insuffisantes pour activer l’enzyme. La présence de AA est indispensable pour le fonctionnement du complexe. L’ordre de fixation des sous unités cytosoliques semble indifférent mais il faut que tous les composants soient présents lors de l’ajout de AA. Enfin, la délétion de p47phox dans la partie C-terminale (aa 343 à 390, domaine d’interaction avec p67phox) il n’y a plus de formation du dimère mais l’enzyme fonctionne normalement. Ces résultats apportent des éléments nouveaux sur le rôle de la dimérisation p47 phox-p67 phox, non indispensable à l’activité du système et sur le rôle mineur de la phosphorylation dans l’activation de la NADPH oxydase in vitroThe NADPH oxidase of phagocytes is an enzyme involved in the innate defense of organisms against pathogens. After phagocyte activation, this enzyme produces superoxide ions by reduction of dioxygen by NADPH. It is constituted of four cytosolic sub-units (p47phox ; p67phox ; p40phox et Rac) and two membrane proteins (gp91 ; p22phox). Its activation takes place through a complex process that involves protein-protein interaction changes leading to assembly and functionning of the catalytic core. In order to obtain information on this process, I have reconstituted the enzyme in a cell free systeme using recombinant proteins, to be able to fully control all the measurement conditions. In this work, we have compared different activation modes of p47phox i) phosphorylation; ii) substitution serine - aspartate by mutations at positions S303, S304 and S328 to mimic phosphorylation; iii) addition of arachidonic acid (AA), a well known activator molecule in vitro. It has been shown that these three activating methods transform p47phox to an open configuration with similar characteristics. However, we have found that the effects of these methods are significantly different. Indeed, the conformational changes observed by circular dichroism are different. For p47phox, the addition of AA destructures the protein. Its phosphorylation induces a bathochromic displacement of the bands, whereas the mutations S-D lead to an opposite displacement. For the dimer p47phox-p67phox , the addition of AA destructures the proteins while mutations induce hardly no changes. We have measured the dissociation constant Kd of the complex p47phox-p67phox. For wild type proteins, Kd value is low (4±2 nM), while mutations of p47phox as well as addition of AA increase its value up to 50 nM, showing a decrease of affinity between p47phox and p67phox. Moreover, on the whole complex, the effect of phosphorylation of p47phox is different from mutations. We have shown that the EC50 values relative to p67phox are sensitive to the various modifications of p47phox. Phosphorylation of p47phox decreases EC₅₀, while double or triple mutations increase its value. We have confirmed that phosphorylation and mutation are not sufficient to activate the enzyme. The presence of AA is a prerequisite for the functionning of the complex, i.e. production of superoxide. The binding order of the cytosolic proteins seems random but it is necessary that all the components be present during the activation by AA. Finally, deletion of the C terminal part of p47phox (aa 343 to 390, interaction domain with p67phox) leads to the absence of dimer formation but does not affect the enzyme activity. These results bring new information on the role of dimerisation of p47-p67 and on that of phosphorylation in the activation of NADPH oxidase in vitro
29
Newcombe, Anthony Richard. « The biochemical role of the small G protein Rac1 in cell signalling pathways : interaction with RhoGDI and the phagocyte NADPH oxidase component, p67'p'h'o'x ». Thesis, University College London (University of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.342224.
Texte intégral
30
Wathne, Gwennaëlle C. L. J. J. « Determining the role of mononuclear phagocyte cell subsets in scrapie transmission from the skin ». Thesis, University of Edinburgh, 2012. http://hdl.handle.net/1842/6489.
Texte intégralRésumé :
Transmissible spongiform encephalopathies (TSEs), or prion diseases, are fatal neurodegenerative diseases that affect several species, such as scrapie in sheep or goats and CJD in humans. In several species, neurological disease is preceded by TSE agent accumulation in lymphoid tissues prior to neuroinvasion. While oral transmission is considered the most common route for scrapie, transmission can also occur through lesions to the skin or mucosa, for example in the mouth or gastrointestinal tract due to rough feed, or birth associated skin damage. Scrapie has also been experimentally transmitted through skin scarification in mice. Following scrapie infection via skin scarification, PrPSc accumulates in the draining lymph node (LN) before spreading to other organs in the lymphoreticular system. It is not yet known by what means the scrapie agent is transported from the skin to the draining LN. Dendritic cells (DCs) in the skin have been found to transport viruses, such as HIV or Dengue, from the skin, thereby raising the question whether DCs or Langerhans cells (LCs), located within the epidermis, play a role in the uptake and transport of the TSE agent from the skin to the draining LN. CD11c is a cell surface marker traditionally used to identify or isolate DCs from other cell types. Mice and rats are naturally resistant to Diphtheria toxin (DTX). A transgenic mouse line was created where the Diphtheria toxin receptor (DTR) was expressed on CD11c+ cells. The presence of this receptor on CD11c+ cells allowed for the temporary conditional depletion of CD11c+ cells following a single injection of DTX. The cells repopulate the tissues within a time frame specific to the tissues the cells are located in. These mice were used to determine whether the absence of CD11c+ cells at the time of scrapie infection via the skin had an effect on the early accumulation of PrPSc within the lymphoid tissues and on disease progression. Immunohistochemical analysis demonstrated that early PrPSc accumulation in the draining LNs was delayed following depletion of CD11c+ cells, indicating that their potential role in the transport of the scrapie agent from the skin. Scrapie incubation period was not affected by the absence of the CD11c+ cells at the time of infection. Recent findings show that CD11c is not exclusive to DCs and is also expressed on macrophage populations. Following DTX-mediated depletion, DCs repopulate the tissues much faster than CD11c+ macrophages. Scrapie infection was carried out in the skin in DTX treated mice after DCs had repopulated the tissues but before macrophage numbers had returned, to determine whether macrophages rather than DCs played a role in the early accumulation of PrPSc in the draining LNs. No differences in PrPSc accumulation were observed in mice depleted of macrophages compared to controls and there was no effect on disease incubation period. Another transgenic mouse line was used, where DTX expression on langerin+ cells (LCs and langerin+ DCs in the dermis), allowed for their temporary depletion through DTX treatment. Following langerin+ cell depletion, increased PrPSc accumulation was observed in the draining LNs 7 weeks post infection, but did not affect the incubation period of disease. These results indicate that the absence of LCs somehow accelerated PrPSc accumulation, and that LCs might play a preventative role in early stages after infection. Histopathological analysis was used to complement microarray studies aimed to determine what immune responses were associated with scarification and DTXmediated depletion of cells within the skin and whether these responses might be linked to disease transmission. DCs and LCs in the skin appear to play different roles in the early stages following scrapie infection via the skin, but the lack of effect on incubation period does not rule out the involvement of other cell types or cell-free mechanisms of scrapie agent spread from the skin.
31
Gilles, K. M. « Molecular mechanisms underlying the control of phagocyte clearance of apoptotic cells ». Thesis, University of Edinburgh, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.651483.
Texte intégralRésumé :
The aim of this thesis was to investigate the molecular mechanisms underlying control of macrophage phagocytosis of apoptotic cells. We have demonstrated that exposure of peripheral blood monocytes to the synthetic glucocorticoid dexamethasone “reprograms” monocyte/macrophage differentiation resulting in a macrophage phenotype with a marked augmentation in the phagocytosis of both apoptotic granulocytes and particles opsonized with low levels of IgG. Increase in phagocytic potential was not mediated by increased expression of putative “phagocytic receptors” proposed to be involved in apoptotic cell clearance. In addition dexamethasone augmentation of apoptotic cell uptake could not be inhibited by blockade of receptor function with either soluble competitive ligands or monoclonal antibodies. Dexamethasone treated macrophages were found to have altered morphology and actin organisation. In particular, loss of “podosome” structures was observed, possibly due to decreased recruitment of adhesion signalling molecules pyk2 and paxillin to focal contacts, and decreased expression of p130cas, a key adaptor molecule in integrin signalling. In addition, glucocorticoid treated cells showed increased activity of the Rho-family GTPase Rac, which has been previously shown to be important for phagocytosis and lamellipodia formation. Expression of p130cas and activation of the mitogen activated protein kinase, ERK are required for migration in a number of different cell types. Basal ERK activity was reduced by dexamethasone-treated monocyte/macrophages. We developed an in vitro “wounding” assay and found that despite the absence of basal ERK activity or p130cas expression in dexamethasone-treated macrophages, these cells were able to migrate.
32
Kelly, Peter M. A. « Investigations of the human mononuclear phagocyte system using the monoclonal antibody EBM/11 ». Thesis, University of Oxford, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.236161.
Texte intégral
33
Davies, Euryl Howell. « An investigation of iron metabolism in cells of the mononuclear phagocyte system ». Thesis, University of Bristol, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.330323.
Texte intégral
34
Buchrieser, Julian. « Understanding human mononuclear phagocyte ontogeny using human induced pluripotent stem cells (iPSCs) ». Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:aaf18203-5f30-4d6a-8f51-3096b29af252.
Texte intégralRésumé :
Tissue-resident macrophages (MΦ) such as microglia, Kupffer and Langerhans cells derive from Myb-independent yolk sac (YS) progenitors generated before the emergence of hematopoietic stem cells (HSCs). Myb-independent YS-derived resident MΦ self-renew locally, independently of circulating adult monocytes and HSCs. In contrast, adult blood monocytes as well as infiltrating, gut and dermal MΦ derive from Myb-dependent HSCs and are less proliferative. These findings are derived from the mouse, using gene knock-outs and lineage tracing, but their applicability to human development has not been formally demonstrated. Here I use a human pluripotent stem cell (hPSC) differentiation model of hematopoiesis, capable of monocyte/MΦ production over prolonged periods of time, as a tool to investigate human mononuclear phagocyte ontogeny. Using a transcriptomic approach I showed that hiPSC-derived monocytes/MΦ (iPS-Mo/MΦ) produced early in differentiation (first weeks) are more proliferative and less immunologically mature than iPS-Mo/MΦ produced at a later time point. I therefore hypothesised either that iPS-Mo/MΦ only become fully mature after several weeks of differentiation or that there are two developmentally distinct waves of MΦ produced over time. By comparing the transcription profile of iPS-Mo/MΦs to that of primary adult blood monocytes and fetal microglia I then showed that early and late iPS-Mo/MΦs were transcriptionally closer to fetal microglia than to adult blood monocytes. To further investigate if iPS-Mo/MΦs are indeed of the same developmental origin as MYB-independent MΦ such as microglia, I used a CRISPR-Cas9 knock-out strategy to show for the first time, that human iPS-Mo/MΦs develop in a MYB-independent, RUNX1 and SPI1 (PU.1)-dependent fashion. This result makes human iPS-Mo/MΦs developmentally related to, and a good model for, MYB-independent tissue-resident \Macros such as alveolar and kidney MΦs, microglia, Kupffer and Langerhans cells. Interestingly, while MYB was not required for the generation of iPS-Mo/MΦs, its knock-out resulted in an increase in iPS-Mo/MΦ production. To investigate this increase I developed two methods for quantifying the differentiation bottleneck occurring during hiPSC differentiation to iPS-Mo/MΦs. Those techniques highlighted a potential increase in progenitor cell generation in MYB KO cells and thus lay foundation to improve our technical understanding of EB differentiation and will enable enhanced manipulation of the EB model.
35
Da, Silva Clément. « Fonction des phagocytes de la plaque de Peyer dans la réponse immunitaire mucosale ». Thesis, Aix-Marseille, 2017. http://www.theses.fr/2017AIXM0251.
Texte intégralRésumé :
Nous avons mis en évidence la présence des phagocytes exprimant le lysozyme dans les Plaque de Peyer chez l’Homme et montré que, comme chez la souris, elles sont principalement localisées dans le SED et sont distinctes des cDC. Dans un deuxième temps, nous avons étudié dans les PP de souris la fonction des différentes populations de phagocytes nouvellement caractérisées. Nous avons en particulier étudié l’impact de la détection d’un acide nucléique d’origine virale par les phagocytes en utilisant un agoniste synthétique du TLR7 : le R848. Bien que TLR7 soit exprimé par les cellules dérivées de monocytes et les DC plasmacytoïdes mais pas par les cDC, nous avons mis en évidence un processus d’activation rapide des cDC impliquant le TNF. Celui-ci conduit à une migration des cDC depuis les villosités adjacentes au dôme vers les IFR et à une forte augmentation de l’expression du CMH-II, des molécules co-stimulatrices ainsi que des gènes dépendants de l’interféron. L’activation du TLR7 induit également une forte expression de la sous unité p40 de l’IL-12 par les LysoDC et certains macrophages. De manière intéressante, nous avons également observé une forte expression d’IL-12 p40 par les LysoDC et certains macrophages peu de temps après le sevrage. Cela nous a conduits à étudier le rôle de cette cytokine dans la mise en place de la réponse immunitaire mucosale. Notre étude a donc des répercussions sur la compréhension des mécanismes conduisant à la mise en place de la réponse immunitaire mucosale en réponse à l’implantation du microbiote intestinal peu de temps après la naissanceIn this study, we first showed that lysozyme expressing cells are found in human PP and share features with their mouse counterpart, such as location and origin. Then, we investigated the behaviour of mouse PP phagocytes upon TLR7 stimulation, using the small synthetic agonist, R848. In PP TLR7 is expressed by monocyte derived cells and plasmacytoid DC, but not by cDC. Nevertheless, TLR7 stimulation triggers a quick activation of cDC. This activation relies on TNF secretion and leads to a massive migration of cDC from the dome associated villi to the IFR and to an increase of MHCII, co-stimulatory molecules and interferon-stimulated gene expression. Stimulation by TLR7 also induces a massive production of IL12p40 by LysoDC and some macrophages. Interestingly, we observed a similar increase of IL-12 p40 production by LysoDC and macrophages shortly after weaning. We thus investigated the impact of Il-12 p40 secretion on the development of the mucosal immune response. Therefore, our study provides clues on the mechanisms involved in the establishment of the mucosal immune response following microbiota colonization
36
Botting, Rachel Anne. « Investigating the phenotype and frequency of mononuclear phagocytes in human skin and anogenital tissue : potential targets to prevent HIV transmission ». Thesis, The University of Sydney, 2016. http://hdl.handle.net/2123/15627.
Texte intégralRésumé :
Mononuclear phagocytes are located throughout the body, and include DCs, macrophages and monocytes. One of their key functions is the detection of pathogens via an array of surface molecules. Determining the repertoire of surface molecules on each subset could reveal targets for DC-based vaccines and potential pathogen interactions. Furthermore, identifying which subsets are present in each of the anogenital tissues may increase understanding of the pathogenesis of various sexually transmitted infections, including HIV. To investigate the phenotype and frequency of mononuclear phagocytes in human skin and anogenital tissue, and their ability to transfer HIV to T cells, cells were isolated by collagenase digestion or after spontaneous migration, and examined by flow cytometry. Two previously undescribed epidermal DC-like subsets were identified in abdominal skin, as well as a novel langerin+ dermal DC. The surface expression of CLRs and Siglecs was observed to differ significantly between the epidermis and dermis, and also between the subsets that reside within each. CD141+ DCs were distinct from other DC subsets, which differed further from macrophage subsets. Greater differences were observed between the subsets isolated from skin compared to those derived in vitro, and between collagenase isolated cells (immature) and spontaneously migrated cells (mature). The subsets isolated from skin were also functionally distinct in their ability to transfer HIV to T cells. Importantly, the frequency of subsets in abdominal skin differed from those found in the anogenital tract, and significant differences in subset ratios were observed between different anogenital tissue types and sites. Therefore, each subset and site represent a unique barrier and/or target for invading pathogens. This work has significant implications for DC-based vaccine design and pathogenesis of infectious agents that interact with mononuclear phagocytes, including HIV and its sexual transmission.
37
Rovere, Querini Patrizia. « Clearance of dying cells by antigen presenting and scavenger phagocytes : implications for autoimmunity and tolerance ». Thesis, Open University, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.323272.
Texte intégral
38
Jakel, Anne. « Role of human lung surfactant proteins A (SP-A) and D (SP-D) in interactions with apoptotic and phagocytic cells ». Thesis, University of Oxford, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.504492.
Texte intégral
39
Zagrajek, Adrian Krzysztof. « Interaction of alphaviruses chikungunya and Semliki Forest with cells of the mononuclear phagocyte system ». Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/25461.
Texte intégralRésumé :
Introduction Chikungunya virus (CHIKV) is an alphavirus in the family Togaviridae. Since 2005 the virus has caused a major epidemic of disease in humans, ranging from Central Africa, South-East Asia, Caribbean and more recently the Americas. The virus is spread by mosquitoes, most notably Aedes aegypti and Ae. albopictus. CHIKV causes an acute disease in humans, which is characterised by a rapid onset of high fever, rash, myalgia and arthralgia. The symptoms typically resolve within a week. Remarkably, up to a third of patients who recover from acute chikungunya develop chronic arthritis/arthralgia, which may last for months or years and has a large negative impact on the quality of life. The mechanism by which this occurs is not yet fully understood. CHIKV can infect human monocytes, and macrophages positive for CHIKV antigen have been observed in joint tissue from patients recovered from acute CHIKV infection but with chronic arthritis. Furthermore, it has been demonstrated that macrophages can be infected with CHIKV in vitro by a mechanism involving apoptotic debris from CHIKV-infected cells. Hypothesis and aims Infection of monocytes and macrophages with CHIKV contributes to clinical disease and virus persistence in vivo. The aim of this project was to investigate the mechanism by which alphaviruses infect macrophages in vitro, and to generate a CHIKV which is unable to replicate in monocytes and macrophages in vitro, and to study its pathogenicity in vivo. Materials and methods HeLa cells were infected with Semliki Forest virus (SFV), an alphavirus closely related to CHIKV, or SFV replicon particles (SFV VRP). Following cell death, whole cell supernatant or clarified cell supernatant from SFV- and SFV VRP-infected cells was passaged onto human monocyte-derived macrophages (MDMs). These cells were observed microscopically for expression of the fluorescent marker encoded by the SFV. Virus and VRP-infected apoptotic debris were inspected for the presence of alphavirus replication complexes by electron microscopy. Subsequently, a recognition element (RE) for a haematopoietic-specific miRNA (miR-142-3P) was incorporated into the genome of SFV (proof-of-concept) and CHIKV to investigate if blocking virus replication in cells of the mononuclear phagocyte system altered virus kinetics in vitro. The replication of the modified viruses was investigated in macrophage/monocyte cell lines Thp-1 and IC-21, and in HEK 293 cells modified to express miR-142-3P under the control of an inducible tetracycline promoter. Modified viruses were tested in animal models of disease (mouse for SFV and non-human primate for CHIKV) to investigate the pathogenicity of these viruses in vivo. Results The presence of apoptotic debris from SFV-infected cells was required to infect MDMs with SFV. The presence or absence of infectious virus particles in the apoptotic debris did not affect the infection rate. Intact alphavirus replication complexes were found within the apoptotic debris. MiR-142-3P RE was successfully incorporated into the genome of both SFV and CHIKV. RE-virus replication in all cells expressing miR-142-3P was reduced by 90-99% when compared to control viruses. RE-virus replication was not affected in cells which did not express miR- 142-3P. In interferon-α/β receptor knockout mice, RE-SFV generated viraemia comparable to the control virus, but could not infect efficiently the population of macrophages resident in the marginal zone of the spleen. RE-CHIKV was found to be genetically stable in vitro following multiple passages on BHK-21 cells in the absence of a selective pressure from miR-142-3P. RE-CHIKV was inoculated into two cynomolgus macaques. The data from this experiment are not yet available. Conclusion SFV was shown to infect MDM via apoptotic debris containing intact alphavirus replication complexes, which were the most likely infectious agent. SFV and CHIKV unable to replicate in haematopoietic cells in vitro were successfully engineered. The pathogenicity of modified SFV and CHIKV was investigated in vivo.
40
Schönheit, Jörg [Verfasser], et Bernd [Akademischer Betreuer] Müller-Röber. « A phagocyte-specific Irf8 gene enhancer establishes early conventional dendritic cell commitment / Jörg Schönheit. Betreuer : Bernd Müller-Röber ». Potsdam : Universitätsbibliothek der Universität Potsdam, 2011. http://d-nb.info/1018122036/34.
Texte intégral
41
Corbin, Alastair Lawrence. « IRF5 directs colonic inflammation and control of mononuclear phagocyte adaptation to the tissue environment ». Thesis, University of Oxford, 2017. http://ora.ox.ac.uk/objects/uuid:fb846ef1-e2a4-476f-a8f8-b52ef776ef41.
Texte intégralRésumé :
Macrophages are leukocytes of the innate immune system that display great phenotypic plasticity to mediate diverse functions. The ontogeny of tissue resident macrophages has been debated in recent decades. It is now recognised that tissue macrophages can be replenished from embryonically-derived precursors, and/or monocyte intermediates in a tissue specific manner. Interferon Regulatory Factor 5 (IRF5) is a transcription factor that promotes a pro-inflammatory phenotype in macrophages in vitro and in vivo. Indeed, IRF5 contributes to the pathogenesis of experimental inflammatory arthritis, lupus, and obesity via recruitment and activation of effector cells. Research described here as part of this thesis, involves the profiling of the intestinal Mononuclear Phagocyte system to investigate the role of IRF5 in the development of monocyte-derived macrophages in the Colonic Lamina Propria (cLP) which are exclusively replenished by adult Ly6Chi monocytes. Using Mixed Bone Marrow Chimaeras (MBMCs) we showed that in shared environment Wild-Type (WT) cLP macrophages dominated IRF5-deficient (Irf5-/-) cLP macrophages in both steady state and inflammation. The development of in vitro bone marrow derived macrophages, and the reconstitution of the haematopoietic compartment in bone marrow of MBMCs were not significantly affected by IRF5 deficiency. IRF5 promoted the accumulation of WT monocytes in the cLP of MBMCs in a process possibly dependent on the CCL2/CCR2 axis. Furthermore, IRF5 expression committed Ly6Chi monocytes to a pro-inflammatory macrophage fate in the inflamed cLP, characterised by protein expression of the cytokines IL1β, and TNFα, and the expression of Ccl4 and Ccl8 transcripts, whilst loss of IRF5 favoured accumulation of CD11b+ IRF4-dependent Dendritic Cells. Of significance, IRF5 expression might have prevented further differentiation of inflammatory macrophages into tissue-resident macrophages, thus supporting an inflammatory state. Irf5-/- mice were protected from Helicobacter hepaticus + αIL10R colitis. Intriguingly, protection from colitis may also be conferred by the presence of Irf5-/- haematopoietic cells, evidenced by WT:Irf5-/- MBMCs . Modulation of IRF5 activity may therefore be a viable therapeutic strategy. RNA sequencing identified that C1q, Cd81, and Ccl8 were upregulated in WT macrophages from MBMC, which may prove therapeutic targets.
42
Banham, Gemma. « Investigation of novel therapeutic strategies in B cell and antibody mediated disease ». Thesis, University of Cambridge, 2019. https://www.repository.cam.ac.uk/handle/1810/286226.
Texte intégralRésumé :
Terminally differentiated B cells are responsible for antibody generation, a key component of adaptive immunity. IgG antibodies play an important role in defence against infection but can be pathogenic in some autoimmune diseases and in solid organ transplantation. In addition to antibody generation, there is increasing interest in the antibody-independent functions of B cells, including their ability to regulate immune responses via the production of IL10. In this thesis I firstly explored the therapeutic potential of belimumab, an anti-BLyS antibody, in an experimental medicine study in kidney transplant recipients. The rationale for this study was based on published studies showing that B cells activate alloreactive T cells and secrete human leukocyte antigen (HLA) and non-HLA antibodies that negatively affect graft function and survival, but may also play a protective role by regulating alloimmune responses promoting transplant tolerance. B-Lymphocyte Stimulator (BLyS) is a cytokine that promotes B cell activation and survival. We performed the first randomized controlled trial using belimumab as early maintenance immunosuppression in kidney transplantation. In belimumab-treated subjects, we demonstrate a reduction in naïve and activated memory B cells, plasmablasts, IgG transcripts in peripheral blood and new antibody formation as well as evidence of reduced CD4 T cell activation and of a skewing of the residual B cell compartment towards an IL10-producing regulatory phenotype. This experimental medicine study highlights the potential of belimumab as a novel therapeutic agent in transplantation. In the second part of my project I performed a preclinical study investigating the potential efficacy of bromodomain inhibitors in reducing antibody-mediated immune cell activation. Immune complexed antigen can activate mononuclear phagocytes (MNP), comprising macrophages and dendritic cells (DCs), via ligation of Fc gamma receptors (FcγR), that bind the Fc region of IgG. FcγR-dependent MNP activation results in profound changes in gene expression that mediate antibody effector function in these cells. The resulting inflammatory response can be pathological in the setting of autoimmune diseases, such as systemic lupus erythematosus and in antibody-mediated rejection in transplantation. BET proteins are a family of histone modification 'readers' that bind acetylated lysine residues within histones and function as a scaffold for the assembly of complexes that regulate gene transcription. Bromodomain inhibitors (I-BET) selectively inhibit the transcription of a subset of inflammatory genes in macrophages following toll-like receptor stimulation. Since MNPs make a key contribution to antibody-mediated pathology, we sought to determine the extent to which I-BET inhibits macrophage and DC activation by IgG. We show that I-BET delays phagolysosome maturation associated with build-up of immune complex (IC) whilst selectively inhibiting IC induced cytokine production. I-BET changed MNP morphology, resulting in a less adherent phenotype, prompting an assessment of its impact on DC migration. In vitro, in a three-dimensional collagen matrix, IgG-IC induced augmentation of DC chemotaxis to chemokine (C-C motif) ligand 19 (CCL19) was abrogated by the addition of I-BET. In vivo, two photon imaging showed that systemic I-BET treatment reduced IC-induced dermal DC mobilisation. Tissue DCs and transferred DC also had reduced migration to draining lymph nodes following I-BET treatment. These observations provide mechanistic insight into the potential therapeutic benefit of I-BET in the setting of antibody-associated inflammation.
43
Tudugalle, Ashanthie R. « C-reactive protein mediated uptake of Neisseria meningitidis into phagocytic cells : the involvement of Fc Gamma receptors and effect on immune responses ». Thesis, University of Surrey, 2016. http://epubs.surrey.ac.uk/809834/.
Texte intégralRésumé :
The human bacterial pathogen Neisseria meningitidis (Nm) is one of the world’s leading causative agents of systemic meningitis, which is characterised by inflammation of the meninges and more rarely, septicaemia. The high mortality rate and debilitating long term effects found in infants and young adults is due to the mounting of a large scale immune response by the host leading to severe inflammation and tissue death. The reasons as to how the meningococcus is able to breach innate immune barriers to cause this kind of infection, however, is still unclear. One important innate immune defence mechanism is the production of acute phase proteins such as C-Reactive Protein (CRP), which is known to opsonise pathogens such as N. meningitidis and enhance its uptake into human phagocytic cells. This investigation has demonstrated the enhanced uptake of CRP opsonised Nm into human macrophages and dendritic cells (DCs); two important innate immune cells which are some of the first to encounter the bacterium upon its dissemination through mucosal epithelium into the blood stream. Not only are these cells important phagocytes needed for the clearance of this pathogen, but dendritic cells in particular are the crucial link to the adaptive immune system, and play an important role in mounting effective, long term immunity to pathogens such as Nm. The enhanced uptake of CRP opsonised Nm was shown to occur by Fc gamma (γ) receptors I and II, which are expressed by both macrophages and dendritic cells. This was demonstrated by the blocking of Fcγ receptors with human IgG and specific antibodies to either receptor, which significantly reduced CRP enhanced uptake. The effect of CRP enhanced uptake of Nm into DC downstream immune responses was investigated to assess if CRP exacerbates or abrogates the hosts inflammatory response to Nm. Both unopsonised and CRP opsonised Nm were able to activate DCs and stimulate the up regulation of co-stimulatory and antigen presentation molecules, which is of significant importance in order to present processed Nm antigens to T cells and mount effective adaptive immune responses. Additionally, unopsonised Nm and CRP opsonised Nm were equally capable of up regulating the secretion of inflammatory cytokines from DCs. This suggests that CRP enhanced uptake of Nm by these phagocytic cells may be beneficial towards the host as despite the increased uptake of Nm by both cell types (potentially for phagocytic clearance), the pro-inflammatory cytokine response by DCs is not further exacerbated, thereby limiting inflammatory damage, which is known to the be the major contributor to the pathogenesis of meningococcal meningitis.
44
Horvath, Dennis John Jr. « The Impact of Phagocyte-UPEC Interactions Upon Pathogenesis of Urinary Tract Infections ». The Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1316282102.
Texte intégral
45
Robertson, Sheona Anne. « Development of a model to study the interaction of Staphylococcus epidermidis with phagocytic cells on the surface of bone and prosthetic joint material ». Thesis, University of Glasgow, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.340257.
Texte intégral
46
Guzmán-Verri, Caterina. « Virulence mechanisms of two Gram negative bacteria : studies on Escherichia coli hemolysin HlyA and on the interaction of Brucella abortus with non-phagocytic cells / ». Stockholm : Karolinska Univ. Press, 2002. http://diss.kib.ki.se/2002/91-7349-114-4.
Texte intégral
47
Lindgren, Helena. « Reactive oxygen and nitrogen in host defence against Francisella tularensis ». Doctoral thesis, Umeå universitet, Klinisk bakteriologi, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-474.
Texte intégralRésumé :
Francisella tularensis, the causative agent of tularemia, is a potent human and animal pathogen. Initially upon infection of the host, intramacrophage proliferation of F. tularensis occurs but after activation of the acquired host immunity, the phagocytes become activated to kill the bacterium. In my thesis, I focused on mechanisms utilized by F. tularensis to survive intracellularly and on host mechanisms responsible for macrophage-mediated killing and control of infection. The F. tularensis-specific protein IglC has been previously shown to be essential to the intramacrophage proliferation and virulence of the bacterium in mice. By electron microscopy of macrophages infected with either the live vaccine strain of F. tularensis or an isogenic mutant, denoted ∆iglC, expression of IglC was found to be necessary for the bacterium to escape from the phagosome. IFN-g-activated macrophages significantly inhibited the escape of the live vaccine strain of F. tularensis from the phagosome. iNOS and phox generate NO and O2-, respectively. These molecules and their reaction products possess both bactericidal and immunoregulatory properties. We investigated the capability of IFN-g-activated peritoneal exudate cells from gene deficient iNOS-/- or p47phox-/- mice to control an intracellular F. tularensis LVS infection. iNOS was found to contribute significantly to the IFN-g induced killing, while phox contributed only to a minor extent. Unexpectedly, bacteria were eradicated even in the absence of both a functional phox and an active iNOS. The eradication was found to depend on ONOO-, the reaction product of NO and O2-, because addition of a decomposition catalyst of ONOO- completely inhibited the killing. Studies on iNOS-/- or p47phox-/- mice infected with F. tularensis LVS showed phox to be important during the first days of infection, a stage when iNOS seemed dispensable. Eventually, iNOS-/- mice died of the infection, suggesting a role of iNOS later in the course of infection. iNOS-/- mice exhibited elevated IFN-g serum levels and severe liver damage suggesting that the outcome of infection was at least in part related to an uncontrolled immune response. Several pathogenic bacteria express Cu,Zn-SOD, which in combination with other enzymes detoxifies reactive oxygen species produced by the host. A deletion mutant of F. tularensis LVS lacking the gene encoding Cu,Zn-SOD was attenuated at least 100-fold compared to LVS in mice. In peritoneal exudate cells from mice, Cu,Zn-SOD was found to be required for effective intramacrophage proliferation and, in mice, important for bacterial replication at the very early phase of infection. In summary, the most conspicuous findings were a capability of IFN-g activated macrophages to retain F. tularensis LVS in the phagosome, an essential role of ONOO- in intracellular killing of F. tularensis, and an importance of Cu,Zn-SOD to the virulence of F. tularensis LVS.
48
Moore, Brian David. « Characterization of the pathogenesis of equine arteritis virus infection of cultured equine mononuclear phagocytes and pulmonary artery endothelial cells / ». For electronic version search Digital dissertations database. Restricted to UC campuses. Access is free to UC campus dissertations, 2003. http://uclibs.org/PID/11984.
Texte intégral
49
Dickey, Laura L. « An Infection Model for Examining the Effects of Gender and Diabetic State on Proinflammatory Cytokine Secretion by Phagocytic Cells in Response to Infection with Burkholderia pseudomallei ». Diss., CLICK HERE for online access, 2007. http://contentdm.lib.byu.edu/ETD/image/etd1825.pdf.
Texte intégral
50
Blagitz, Maiara Garcia. « Avaliação funcional dos fagócitos sanguíneos e lácteos de vacas naturalmente infectadas pelo vírus da leucose dos bovinos ». Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/10/10136/tde-04042011-110123/.
Texte intégralRésumé :
O vírus da leucose enzoótica bovina (VLEB) pode interferir na proporção e na funcionalidade dos linfócitos B e das demais células sanguíneas. Acreditando-se que essas alterações pudessem interferir nos mecanismos de defesa da glândula mamária, o presente estudo avaliou funcionalmente os fagócitos sanguíneos e lácteos de vacas naturalmente infectadas pelo VLEB, por meio da expressão de diferentes receptores de superfície celular de fagócitos e linfócitos; da morte celular dos fagócitos e do linfócito B; pelo potencial de fagocitose e produção intracelular de peróxido de hidrogênio pelas células CD14+ e CH138+. Foram selecionadas nove vacas negativas para a LEB (grupo negativo), dez positivas sem linfocitose (grupo AL) e seis positivas com linfocitose persistente (grupo LP). Independente do perfil hematológico das vacas positivas para a LEB, nas amostras de sangue foram observadas menor expressão de células mononucleares CD14+, de linfócitos T (CD3+) e de linfócitos B CD21+ CD11b+ e maior expressão de linfócitos B (CD21+). As vacas do grupo LP apresentaram menores quantidades de linfócitos T auxiliares (CD3+ CD4+) e de linfócitos B CD21+ CD5- CD11b- e maiores quantidades de linfócitos B CD21+ CD5+ CD11b+. Menores quantidades de linfócitos B CD21+ CD5+ foram observados nas vacas do grupo AL do que nas vacas do grupo negativo. As vacas do grupo LP apresentaram menores índices de fagocitose por Escherichia coli pelas células mononucleares CD14+, menor produção de peróxido de hidrogênio e menores índices de fagocitose por Staphylococcus aureus pelas células polimorfonucleares CH138+. As vacas do grupo LP apresentaram menores índices de necrose, de apoptose e/ou necrose e maior viabilidade das células mononucleares CD14+, das células polimorfonucleares CH138+ e dos linfócitos B (CD21+). Apenas os linfócitos B (CD21+) das vacas do grupo LP apresentaram menores índices de morte por apoptose, e as células mononucleares CD14+ das vacas do grupo AL manifestaram maiores índices de apoptose e/ou necrose do que as vacas negativas. Independente do perfil hematológico das vacas, nas amostras de leite foram observadas maiores quantidades de macrófagos e maiores expressões de linfócitos T (CD3+) e de linfócitos B (CD21+). As vacas do grupo AL apresentaram maior quantidade de linfócitos B (CD21+) do que as vacas negativas. As vacas do grupo LP apresentaram menores quantidades de linfócitos T citotóxicos (CD3+ CD8+), de linfócitos B CD21+ CD11b+ e de linfócitos B CD21+ CD5+ CD11b+ e maior quantidade de linfócitos B CD21+ CD5- CD11b-. As vacas do grupo AL apresentaram menores índices de fagocitose por Escherichia coli pelos macrófagos CD14+ e pelos leucócitos CH138+ e as vacas do grupo LP apresentaram maior produção de peróxido de hidrogênio intracelular. As vacas positivas para LEB apresentaram maiores índices de morte por necrose dos macrófagos CD14+ e dos linfócitos B (CD21+) e menores índices de morte por apoptose dos macrófagos CD14+, dos leucócitos CH138+ e dos linfócitos B (CD21+). Estas vacas também apresentaram maior viabilidade dos macrófagos CD14+ e dos leucócitos CH138+. As vacas do grupo LP apresentaram maiores índices de apoptose e/ou necrose dos macrófagos CD14+, de necrose de leucócitos CH138+ e de viabilidade de linfócitos B (CD21+). Resultados permitem concluir que a o VLEB altera a resposta imune da glândula mamária.The enzootic bovine leukemia virus (BLV) can influence the amount of lymphocytes B and other blood cells and their functions. Believing that these changes could interfere in the defense mechanisms of the mammary gland, this study evaluated blood and milk phagocytes functions from cows naturally infected VLEB through the expression of different cell surface receptors of phagocytes and lymphocytes; from death cell of phagocytes and B lymphocytes; the phagocytosis and intracellular production of hydrogen peroxide by CD14+ and CH138+ cells. We chose nine cows negative for the LEB (negative group), ten positive without lymphocytosis (LA group) and six positive with persistent lymphocytosis (LP group). In blood samples of positive cows for BLV, it was observed smaller expression of CD14+ mononuclear, T lymphocytes (CD3+) and CD21+ CD11b+ B lymphocytes, along with increased expression of B lymphocytes (CD21+). Cows of the LP group had lower amounts of T helper lymphocytes (CD3+ CD4+) and CD21+ CD5- CD11b- B lymphocytes and higher amounts of CD21+ CD5+ CD11b+ B lymphocytes. In cows of AL group it was observed lower amounts of CD21+ CD5+ B lymphocytes than in cows of negative group. Cows of LP group had lower rates of Escherichia coli phagocytosis by CD14+ mononuclear cells, lower intracellular production of hydrogen peroxide and lower rates of phagocytosis of Staphylococcus aureus by CH138+ polymorphonuclear cells. Cows of LP group showed less necrosis, apoptosis and/or necrosis and increased viability of CD14+ mononuclear cells, CH138+ polymorphonuclear cells and B lymphocytes (CD21+). Only the B-lymphocytes (CD21+) of the cows in the LP group showed less apoptosis, and CD14 + mononuclear cells from cows in the AL group showed higher rates of apoptosis and/or necrosis than the ones from negative cows. In the milk sample, the positive cows showed higher amounts of macrophages and increased expression of T lymphocytes (CD3+) and B lymphocytes (CD21+). Cows of AL group showed a higher amount of B lymphocytes (CD21+) than negative cows. Cows of LP group had lower amounts of T cytotoxic lymphocytes (CD3+, CD8+), CD21+ CD11b+ B lymphocytes and CD21+, CD5+, CD11b+, B lymphocytes and increased amount of CD21 + CD5- CD11b- B lymphocytes. Cows of the AL group had lower rates of Escherichia coli phagocytosis by CD14+ macrophages and CH138+ leukocytes and cows of group LP had higher production of intracellular hydrogen peroxide. The positive cows for LEB had higher rates of death by necrosis of CD14+ macrophages and B lymphocytes (CD21+) and lower rates of apoptosis of CD14+ macrophages, CH138+ leukocytes and B lymphocytes (CD21+). These cows also had higher viability of CD14+ macrophages and CH138+ leukocytes. Cows on the LP group had higher rates of apoptosis and/or necrosis of CD14+ macrophages, necrosis of CH138+ leukocytes and viability of B lymphocytes (CD21+). Results suggested that the VLEB influence the immune response of the mammary gland.