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Статті в журналах з теми "Mtb Infection"
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Dempsey, Laurie A. "CD153 combats Mtb infection." Nature Immunology 19, no. 11 (October 17, 2018): 1148. http://dx.doi.org/10.1038/s41590-018-0246-4.
Повний текст джерела
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Rosas Mejia, Oscar, Erin S. Gloag, Jianying Li, Marisa Ruane-Foster, Tiffany A. Claeys, Daniela Farkas, Shu-Hua Wang, Laszlo Farkas, Gang Xin, and Richard T. Robinson. "Mice infected with Mycobacterium tuberculosis are resistant to acute disease caused by secondary infection with SARS-CoV-2." PLOS Pathogens 18, no. 3 (March 24, 2022): e1010093. http://dx.doi.org/10.1371/journal.ppat.1010093.
Повний текст джерелаАнотація:
Mycobacterium tuberculosis (Mtb) and SARS-CoV-2 (CoV2) are the leading causes of death due to infectious disease. Although Mtb and CoV2 both cause serious and sometimes fatal respiratory infections, the effect of Mtb infection and its associated immune response on secondary infection with CoV2 is unknown. To address this question we applied two mouse models of COVID19, using mice which were chronically infected with Mtb. In both model systems, Mtb-infected mice were resistant to the pathological consequences of secondary CoV2 infection, and CoV2 infection did not affect Mtb burdens. Single cell RNA sequencing of coinfected and monoinfected lungs demonstrated the resistance of Mtb-infected mice is associated with expansion of T and B cell subsets upon viral challenge. Collectively, these data demonstrate that Mtb infection conditions the lung environment in a manner that is not conducive to CoV2 survival.
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Olive, Andrew J., Clare M. Smith, Christina E. Baer, Jörn Coers, and Christopher M. Sassetti. "Mycobacterium tuberculosis Evasion of Guanylate Binding Protein-Mediated Host Defense in Mice Requires the ESX1 Secretion System." International Journal of Molecular Sciences 24, no. 3 (February 2, 2023): 2861. http://dx.doi.org/10.3390/ijms24032861.
Повний текст джерелаАнотація:
Cell-intrinsic immune mechanisms control intracellular pathogens that infect eukaryotes. The intracellular pathogen Mycobacterium tuberculosis (Mtb) evolved to withstand cell-autonomous immunity to cause persistent infections and disease. A potent inducer of cell-autonomous immunity is the lymphocyte-derived cytokine IFNγ. While the production of IFNγ by T cells is essential to protect against Mtb, it is not capable of fully eradicating Mtb infection. This suggests that Mtb evades a subset of IFNγ-mediated antimicrobial responses, yet what mechanisms Mtb resists remains unclear. The IFNγ-inducible Guanylate binding proteins (GBPs) are key host defense proteins able to control infections with intracellular pathogens. GBPs were previously shown to directly restrict Mycobacterium bovis BCG yet their role during Mtb infection has remained unknown. Here, we examine the importance of a cluster of five GBPs on mouse chromosome 3 in controlling Mycobacterial infection. While M. bovis BCG is directly restricted by GBPs, we find that the GBPs on chromosome 3 do not contribute to the control of Mtb replication or the associated host response to infection. The differential effects of GBPs during Mtb versus M. bovis BCG infection is at least partially explained by the absence of the ESX1 secretion system from M. bovis BCG, since Mtb mutants lacking the ESX1 secretion system become similarly susceptible to GBP-mediated immune defense. Therefore, this specific genetic interaction between the murine host and Mycobacteria reveals a novel function for the ESX1 virulence system in the evasion of GBP-mediated immunity.
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Wong, Eileen A., Carolyn Kraus, Keith A. Reimann, and JoAnne L. Flynn. "The role of IL-10 during early M. tuberculosis infection in a non-human primate model." Journal of Immunology 198, no. 1_Supplement (May 1, 2017): 123.5. http://dx.doi.org/10.4049/jimmunol.198.supp.123.5.
Повний текст джерелаАнотація:
Abstract Tuberculosis (TB), caused by M. tuberculosis (Mtb), continues to be a global health problem. Lung granulomas, organized structures of host immune cells to contain Mtb, are the pathologic hallmark of TB. T cell cytokines play a major role in containment of Mtb infection within these granulomas. While the importance of pro-inflammatory cytokines IFN-γ and TNF in controlling Mtb infections has been established, the effects of immunomodulatory cytokines, such as IL-10, in Mtb infections are less well understood. We used cynomolgus macaques, a non-human primate (NHP) model that recapitulates human TB to investigate the role of IL-10 early in Mtb infection. Preliminary ex vivo studies of excised lung granulomas from Mtb-infected NHPs suggested IL-10 may be downregulating IL-2 cytokine production in TB lung granulomas. To further examine the role of IL-10, a cross-reactive, rhesus recombinant anti-IL-10 antibody was used to neutralize IL-10 in vivo in NHPs prior to and during the course of Mtb infection. Peripheral cytokine responses in the presence of IL-10 neutralization were analyzed serially by flow cytometry of peripheral blood mononuclear cells. Disease progression was monitored by PET-CT scans, and local immune responses in the granulomas assessed at necropsy. Our data indicate transient differences in inflammation early in infection between anti-IL-10-treated and control monkeys. Surprisingly, there was less inflammation in granulomas from IL-10 neutralized animals at 3–4 weeks post-infection, compared to control animals. Overall, this unique dataset provides important insight into the contribution of IL-10 to the necessary immunological balance for controlled bacterial burden and disease pathology in Mtb infections.
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Kieswetter, Nathan S., Mumin Ozturk, Lerato Hlaka, Julius Ebua Chia, Ryan J. O. Nichol, Jasmine M. Cross, Leah M. C. McGee, et al. "Intranasally administered S-MGB-364 displays antitubercular activity and modulates the host immune response to Mycobacterium tuberculosis infection." Journal of Antimicrobial Chemotherapy 77, no. 4 (January 25, 2022): 1061–71. http://dx.doi.org/10.1093/jac/dkac001.
Повний текст джерелаАнотація:
Abstract Background Previously, we evaluated the intracellular mycobactericidal activity of the minor groove binder, S-MGB-364 against the clinical Mycobacterium tuberculosis (Mtb) strain HN878 in macrophages. Objectives To assess the mycobactericidal activity of S-MGB-364 in Mtb-infected mice. Further, we investigated a plausible DNA binding mechanism of action of S-MGB-364. Methods The anti-TB and host immune effects of intranasal S-MGB-364 or S-MGB-364 encapsulated in non-ionic surfactant vesicles (NIV) were assessed in Mtb-infected mice by cfu enumeration, ELISA, histology, and flow cytometry. DNA binding was examined using native mass spectrometry and UV-vis thermal melt determination. S-MGB interference with DNA-centric biological events was assessed using a representative panel of Mtb and human topoisomerase I, and gyrase assays. Results S-MGB-364 bound strongly to DNA as a dimer, significantly increasing the stability of the DNA:S-MGB complex compared with DNA alone. Moreover, S-MGB-364 inhibited the relaxation of Mtb topoisomerase I but not the human form. In macrophages, S-MGB-364 or S-MGB-364-NIV did not cause DNA damage as shown by the low γ-H2AX expression. Importantly, in the lungs, the intranasal administration of S-MGB-364 or S-MGB-364-NIV formulation in Mtb-infected mice was non-toxic and resulted in a ∼1 log cfu reduction in mycobacterial burden, reduced the expression of proinflammatory cytokines/chemokines, altered immune cell recruitment, and importantly reduced recruitment of neutrophils. Conclusions Together, these data provide proof of concept for S-MGBs as novel anti-TB therapeutics in vivo.
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Wong, Kevin, James Nguyen, Lillie Blair, Marina Banjanin, Bunraj Grewal, Shane Bowman, Hailey Boyd, et al. "Pathogenesis of Human Immunodeficiency Virus-Mycobacterium tuberculosis Co-Infection." Journal of Clinical Medicine 9, no. 11 (November 6, 2020): 3575. http://dx.doi.org/10.3390/jcm9113575.
Повний текст джерелаАнотація:
Given that infection with Mycobacterium tuberculosis (Mtb) is the leading cause of death amongst individuals living with HIV, understanding the complex mechanisms by which Mtb exacerbates HIV infection may lead to improved treatment options or adjuvant therapies. While it is well-understood how HIV compromises the immune system and leaves the host vulnerable to opportunistic infections such as Mtb, less is known about the interplay of disease once active Mtb is established. This review explores how glutathione (GSH) depletion, T cell exhaustion, granuloma formation, and TNF-α upregulation, as a result of Mtb infection, leads to an increase in HIV disease severity. This review also examines the difficulties of treating coinfected patients and suggests further research on the clinical use of GSH supplementation.
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Bian, Yao, Shaobin Shang, Sharmila Shanmuganad, Sarah Siddiqui, and Chyung-Ru Wang. "Qa-1b has antigen presentation and immunoregulatory roles during aerogenic Mycobacterium tuberculosis infection (P3296)." Journal of Immunology 190, no. 1_Supplement (May 1, 2013): 134.1. http://dx.doi.org/10.4049/jimmunol.190.supp.134.1.
Повний текст джерелаАнотація:
Abstract The mouse MHC Ib molecule Qa-1b plays roles in both antigen presentation and immune regulation in different disease models. Further, the human homologue of Qa-1b, HLA-E, can present Mycobacterium tuberculosis (Mtb) peptides to CD8+ T cells. In viral infections, Qa-1b suppresses NK and CD8+ T cell function by interacting with inhibitory CD94/NKG2A molecules. In addition, Qa-1b can activate CD8+ T regulatory cells, which suppress CD4+ T cell responses in EAE. However, the role of Qa-1b in Mycobacterium tuberculosis (Mtb) infection is unknown. In this study, we find Qa-1b expression is upregulated in a mouse model of low-dose, aerogenic infection with Mtb. We find that Qa-1b, like HLA-E, can bind a number of Mtb peptides; a subset of these peptides are recognized by CD8+ T cells and induce IFN-γ production during aerogenic Mtb infection. To determine the overall contribution of Qa-1b to Mtb infection, we infected Qa-1b-deficient and wild-type mice. Qa-1b-deficient mice had increased production of pro-inflammatory cytokines compared to wild-type, indicating Qa-1b plays a regulatory role in Mtb infection. Infected Qa-1b-deficient mice also show increased expression of CD94/NKG2A on CD8+ T cells, indicating a potential mechanism by which Qa-1b controls immune responses in Mtb infection. Our data suggest that during Mtb infection, Qa-1b is uniquely able to both activate immune responses through antigen presentation as well as suppress immune responses via regulatory mechanisms.
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He, Xianbao, Jared J. Eddy, Karen R. Jacobson, Andrew J. Henderson, and Luis M. Agosto. "Enhanced Human Immunodeficiency Virus-1 Replication in CD4+ T Cells Derived From Individuals With Latent Mycobacterium tuberculosis Infection." Journal of Infectious Diseases 222, no. 9 (May 16, 2020): 1550–60. http://dx.doi.org/10.1093/infdis/jiaa257.
Повний текст джерелаАнотація:
Abstract Background Mycobacterium tuberculosis (Mtb) and human immunodeficiency virus (HIV) coinfection increases mortality, accelerates progression to acquired immune deficiency syndrome, and exacerbates tuberculosis disease. However, the impact of pre-existing Mtb infection on subsequent HIV infection has not been fully explored. We hypothesized that Mtb infection creates an immunological environment that influences the course of HIV infection, and we investigated whether pre-existing Mtb infection impacts the susceptibility of CD4+ T cells to HIV-1 infection. Methods Plasma and blood CD4+ T cells isolated from HIV-negative individuals across the Mtb infection spectrum and non-Mtb-infected control individuals were analyzed for inflammation markers and T-cell phenotypes. CD4+ T cells were infected with HIV-1 in vitro and were monitored for viral replication. Results We observed differences in proinflammatory cytokines and the relative proportion of memory T-cell subsets depending on Mtb infection status. CD4+ T cells derived from individuals with latent Mtb infection supported more efficient HIV-1 transcription, release, and replication. Enhanced HIV-1 replication correlated with higher percentages of CD4+ TEM and TTD cells. Conclusions Pre-existing Mtb infection creates an immunological environment that reflects Mtb infection status and influences the susceptibility of CD4+ T cells to HIV-1 replication. These findings provide cellular and molecular insights into how pre-existing Mtb infection influences HIV-1 pathogenesis.
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Moriarty, Ryan V., Amy L. Ellis, and Shelby L. O’Connor. "Monkeying around with MAIT Cells: Studying the Role of MAIT Cells in SIV and Mtb Co-Infection." Viruses 13, no. 5 (May 8, 2021): 863. http://dx.doi.org/10.3390/v13050863.
Повний текст джерелаАнотація:
There were an estimated 10 million new cases of tuberculosis (TB) disease in 2019. While over 90% of individuals successfully control Mycobacterium tuberculosis (Mtb) infection, which causes TB disease, HIV co-infection often leads to active TB disease. Despite the co-endemic nature of HIV and TB, knowledge of the immune mechanisms contributing to the loss of control of Mtb replication during HIV infection is lacking. Mucosal-associated invariant T (MAIT) cells are innate-like T cells that target and destroy bacterially-infected cells and may contribute to the control of Mtb infection. Studies examining MAIT cells in human Mtb infection are commonly performed using peripheral blood samples. However, because Mtb infection occurs primarily in lung tissue and lung-associated lymph nodes, these studies may not be fully translatable to the tissues. Additionally, studies longitudinally examining MAIT cell dynamics during HIV/Mtb co-infection are rare, and lung and lymph node tissue samples from HIV+ patients are typically unavailable. Nonhuman primates (NHP) provide a model system to characterize MAIT cell activity during Mtb infection, both in Simian Immunodeficiency Virus (SIV)-infected and SIV-naïve animals. Using NHPs allows for a more comprehensive understanding of tissue-based MAIT cell dynamics during infection with both pathogens. NHP SIV and Mtb infection is similar to human HIV and Mtb infection, and MAIT cells are phenotypically similar in humans and NHPs. Here, we discuss current knowledge surrounding MAIT cells in SIV and Mtb infection, how SIV infection impairs MAIT cell function during Mtb co-infection, and knowledge gaps to address.
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Nusbaum, Rebecca, Matthew Huante, Putri Sutjita, Veronica Calderon, Sudhamathi Vijayakumar, Judith Aronson, Robert Hunter, et al. "HIV-1 promotes neutrophil infiltration and lung damage in humanized mice co-infected with Mycobacterium tuberculosis (HUM1P.266)." Journal of Immunology 194, no. 1_Supplement (May 1, 2015): 52.15. http://dx.doi.org/10.4049/jimmunol.194.supp.52.15.
Повний текст джерелаАнотація:
Abstract Co-infection with human immunodeficiency virus (HIV) and Mycobacterium tuberculosis (Mtb) promotes aggressive disease through mechanisms that are poorly understood. A recent study suggests an association between peripheral blood neutrophil count and Mtb load in the sputum of human subjects with HIV co-infection. We used our humanized BLT mouse (HuMouse) model of HIV/Mtb co-infection as an investigative tool to study the role of neutrophils in co-infection pathobiology. Humanized mice were infected intravenously with HIV-1 for 3 weeks and then co-infected intranasally with Mtb. Compared to HuMice with Mtb or HIV mono-infections, increased neutrophil numbers were observed in the lungs of co-infected animals, as determined by detection of myeloperoxidase using immunohistochemistry. Consistent with the role of neutrophils to promote immune-mediated pathology in TB disease, greater tissue necrosis and increased mycobacterial burden was observed in the lungs of co-infected animals. In support of these findings, an increased pulmonary production of cytokines and chemokines associated with neutrophil recruitment including IL-8, CXCL5, fractalkine, and IL-17 were also observed in co-infected animals. These studies identify mechanisms for immune-mediated pathology due to HIV/Mtb co-infection that can be targeted to restore immune balance in the lung and complement antimycobacterials.
Дисертації з теми "Mtb Infection"
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Jones, Shelby-Sara Ann. "The role of Lymphoblastic leukemia 1 (Lyl1) in Mycobacterium tuberculosis (Mtb) infection." Doctoral thesis, Faculty of Health Sciences, 2021. http://hdl.handle.net/11427/33727.
Повний текст джерелаАнотація:
Lymphoblastic leukemia 1 (Lyl1) is a well-studied transcription factor known to exhibit oncogenic potential during various forms of leukemia. Since its discovery in 1989, many reports have been published describing its relationship with cancer as well as demonstrating its function during hematopoiesis. Lyl1 has been shown to serve a significant role during thymopoiesis by contributing to T-cell development. However, it has been recently reported that irrespective of its significance during T-cell development, mature comparable single positive T-cells are observed in mouse models. The use of murine models has been crucial in identifying potential targets for host-directed therapies (HDT) which has been shown to provide great potential in treating tuberculosis (TB). It is evident that Mycobacterium tuberculosis (Mtb), the causative agent for TB, is capable of developing resistance to various treatments that target the bacterium itself. Therefore, by designing therapies that directly target host factors could assist in circumventing Mtb resistance. By analyzing Mtb-infected bone marrow-derived macrophages (BMDM) that have been subjected to genome-wide transcriptional deep sequencing of total RNA using a single molecule sequencer in conjunction with the cap analysis gene expression (CAGE) technique, various differentially expressed genes were identified, including the oncogenic transcription factor, Lyl1. With the use of murine models, we investigated whether Lyl1 is important for various immunological responses at steady state, the regulation of Lyl1 in response to various immune stimulants including LPS and whether this transcription factor is relevant in bacterial infections including Listeria monocytogenes (Lm) and Mtb. The data in this thesis demonstrate comparable immunological responses, including cellular recruitment by means of flow cytometry and cytokine responses by means of ELISA, between naïve littermate control and Lyl1-deficient mice. Further evaluation of Lyl1 regulation revealed the influence of MAPk and NFκB signaling on Lyl1 expression upon LPS stimulation by significantly downregulating this transcription factor in immune stimulated macrophages. A role for Lyl1 during bacterial infections was observed in Lm-infected mice whereby Lyl1-/- mice succumbed earlier to listeriosis compared to the littermate controls. We further established a functional role for this transcription factor during Mtb infection in vitro and in vivo. The early surrender of Lyl1-deficient mice to Mtb HN878 infection, accompanied by increased bacterial burden during chronic Mtb infection, demonstrated enhanced susceptibility in the absence of Lyl1. We show that Lyl1-deficient host susceptibility is a consequence of enhanced inflammatory responses and increased bacterial growth. This is demonstrated by increased neutrophilic inflammation, pro-inflammatory cytokine and chemokine secretion along with a reduction in anti-inflammatory cytokine release during chronic Mtb infection. Here, we demonstrate the first non-leukemia role for Lyl1 by suggesting a role and requirement for this transcription factor during bacterial infections. Given the significant role during Mtb infection, our studies suggest the use of Lyl1 associated pathways as a potential HDT target for TB.
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Rothchild, Alissa Chen. "Antimicrobial Roles for iNKT Cells and GM-CSF in Mycobacterium Tuberculosis Infection." Thesis, Harvard University, 2014. http://dissertations.umi.com/gsas.harvard:11371.
Повний текст джерелаАнотація:
Despite effective antibiotics, Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, still infects nearly one-third of the world's population. While key immune factors including CD4+ T cells and IFNg production have been identified, there are still many antimicrobial mechanisms yet to be explored. Here we characterized the role of invariant natural killer T (iNKT) cells and GM-CSF during Mtb infection.
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Benet, Garrabé Susana. "Impact of a SIGLEC1 null variant on the pathogenesis of HIV-1 and Mtb infection." Doctoral thesis, Universitat Autònoma de Barcelona, 2021. http://hdl.handle.net/10803/671930.
Повний текст джерелаАнотація:
Les cèl·lules presentadores d’antigen de llinatge mieloide tenen la capacitat de respondre a una infecció d’una manera ràpida i eficient coordinant respostes immunitàries innates i adaptatives. Malgrat això, en el cas de la infecció pel virus de la immunodeficiència humana de tipus 1 (VIH-1), aquestes cèl·lules poden contribuir a la patogènesi viral a través de la captura i la transmissió de partícules virals a les cèl·lules diana, un procés conegut com trans-infecció. Aquest mecanisme depèn de Siglec-1 (CD169), un receptor de membrana de les cèl·lules mieloides que reconeix gangliòsids sialilats presents a la membrana del virus. Per tal d’analitzar in vivo la contribució de la trans-infecció en la patogènesi del VIH-1, vam buscar individus SIGLEC1-deficients i vam identificar 85 individus heterozigots i 2 homozigots per una variant de pèrdua de funció que aboleix l’expressió de Siglec-1. De manera rellevant, les cèl·lules d’aquests individus mancaven de l’activitat de Siglec-1 en relació a la captura i la transmissió del VIH-1. Malgrat aquest fenotip, no vam observar diferències prominents pel què fa a la susceptibilitat a la infecció per VIH-1 ni a la progressió cap a la síndrome d’immunodeficiència adquirida (SIDA) en els individus portadors d’aquesta variant de SIGLEC1. Malgrat tot, l’anàlisi de l’efecte del truncament de Siglec-1 en la progressió a SIDA no va ser concloent degut a la mida limitada de la cohort, la manca d’una història clínica complerta amb informació sobre la data de seroconversió, la restricció d’estudiar només períodes sense tractament i la co-infecció amb patògens addicionals que podrien influenciar el fenotip observat en la direcció oposada al que s’esperava.
De fet, aquesta darrera limitació ens va portar a investigar l’efecte de la variant SIGLEC1-deficient en les co-infeccions associades al VIH-1 i vam trobar una associació significativa entre aquesta variant i la disseminació extrapulmonar de Mycobacterium tuberculosis (Mtb) en dues cohorts clíniques que inclouen 6,256 individus. Quan vam analitzar l’absència de Siglec-1 en un model murí, els ratolins knockout per Siglec-1 van presentar una propagació local de bacteris al pulmó i malgrat tenir una càrrega bacil·lar similar, van desenvolupar lesions més extenses en comparació amb els ratolins salvatges. A més a més, vam demostrar que Siglec-1 és necessari per tal d’induir la presentació d’antígens a través de la captura de vesícules extracel·lulars. Proposem un model on l’absència de Siglec-1 endarrereix l’inici d’una immunitat que protegeix enfront el micobacteri limitant l’intercanvi d’antígens mitjançant vesícules extracel·lulars, permetent així una propagació local del micobacteri que incrementa el risc d’una disseminació extrapulmonar. En resum, al llarg d’aquesta tesi hem explorat el concepte d’antagonisme pleiotròpic en individus co-infectats portadors de la variant SIGLEC1-deficient, on l’alteració del control immunitari del micobacteri en absència de Siglec-1 podria influenciar el curs clínic dels individus infectats pel VIH-1, emmascarant així els beneficis esperats d’aquesta variant en retardar la progressió a SIDA.Las células presentadoras de antígeno de linaje mieloide tienen la capacidad de responder a una infección de una manera rápida y eficiente coordinando respuestas inmunes innatas y adaptativas. Sin embargo, en el caso de la infección por el virus de la inmunodeficiencia humana de tipo 1 (VIH-1), estas células pueden contribuir en la patogénesis viral a través de la captura y la transmisión de partículas virales a las células diana, un proceso conocido como trans-infección. Este mecanismo depende de Siglec-1 (CD169), un receptor de membrana de las células mieloides que reconoce gangliósidos sialidados presentes en la membrana del virus. Para analizar in vivo la contribución de la trans-infección en la patogénesis del VIH-1, buscamos individuos SIGLEC1-deficientes e identificamos 85 individuos heterocigotos y 2 homocigotos para una variante de pérdida de función que suprime la expresión de Siglec-1. De manera relevante, las células de estos individuos carecían de la actividad de Siglec-1 en relación a la captura y la transmisión del VIH-1. A pesar de este fenotipo, no hemos observado diferencias prominentes con respecto a la susceptibilidad a la infección por VIH-1 ni a la progresión hacia el síndrome de inmunodeficiencia adquirida (SIDA) en los individuos portadores de esta variante de SIGLEC1. A pesar de ello, el análisis del efecto del truncamiento de Siglec-1 en la progresión a SIDA no resultó concluyente debido al tamaño limitado de la cohorte, la falta de una historia clínica completa con información sobre la fecha de seroconversión, la restricción de estudiar solamente períodos sin tratamiento y la co-infección con patógenos adicionales que podrían influenciar el fenotipo observado en la dirección opuesta a lo esperado. De hecho, esta última limitación nos llevó a investigar el efecto de la variante SIGLEC1-deficiente en las co-infecciones asociadas al VIH-1 y encontramos una asociación significativa entre esta variante y la diseminación extrapulmonar de Mycobacterium tuberculosis (Mtb) en dos cohortes clínicas que incluyen 6,256 individuos. Cuando analizamos la ausencia de Siglec-1 en un modelo murino, los ratones knockout para Siglec-1 presentaron una propagación local de bacterias en el pulmón y a pesar de tener una carga bacilar similar, desarrollaron lesiones más extensas en comparación con los ratones salvajes. Además, hemos demostrado que Siglec-1 es necesario para inducir la presentación de antígenos a través de la captura de vesículas extracelulares. Proponemos un modelo en el que la ausencia de Siglec-1 retrasa el inicio de una inmunidad que protege frente la micobacteria limitando el intercambio de antígenos mediante vesículas extracelulares, permitiendo así una propagación local de la micobacteria que incrementa el riesgo de una diseminación extrapulmonar. En resumen, a lo largo de esta tesis hemos explorado el concepto de antagonismo pleiotrópico en individuos co-infectados portadores de la variante SIGLEC1-deficiente, donde la alteración del control inmune de la micobacteria en ausencia de Siglec-1 podría influenciar el curso clínico de los individuos infectados por VIH-1, enmascarando así los beneficios esperados de esta variante en el retraso de la progresión a SIDA.
Antigen presenting cells of the myeloid lineage have the ability to respond rapidly and effectively to infection by coordinating innate and adaptive immune responses. However, in the case of human immunodeficiency virus type 1 (HIV-1) infection, these cells might contribute to viral pathogenesis through the capture and transmission of infectious viral particles to target cells, a process known as trans-infection. This mechanism depends on Siglec-1 (CD169), a myeloid-cell surface receptor that recognizes sialylated gangliosides present on the viral membrane. To dissect the contribution of trans-infection in HIV-1 pathogenesis in vivo, we searched for SIGLEC1 null individuals and identified 85 heterozygous and 2 homozygous people with a loss-of-function variant that abrogates Siglec-1 expression. Importantly, cells from these individuals were defective for Siglec-1 activity in HIV-1 capture and transmission. Despite this phenotype, we did not observe prominent differences on HIV-1 susceptibility nor progression to acquired immunodeficiency syndrome (AIDS) in individuals harboring the SIGLEC1 null variant. Nonetheless, analysis of the effect of Siglec-1 truncation on progression to AIDS was not conclusive due to the limited cohort size, the lack of complete clinical records such as the seroconversion date, the restriction to study only off-therapy periods, and the co-infection with additional pathogens that might influence the observed phenotype in the opposite direction from what was expected. As a matter of fact, the latest limitation prompted us to investigate the effect of the SIGLEC1 null variant in HIV-1 co-infections and we found a significant association between this variant and extrapulmonary dissemination of Mycobacterium tuberculosis (Mtb) in two clinical cohorts comprising 6,256 individuals. When we analyzed the absence of Siglec-1 in a murine model, local spread of bacteria within the lung was apparent in Mtb-infected Siglec-1 knockout mice which, despite having similar bacterial load, developed more extensive lesions compared to wild type mice. Moreover, we demonstrated that Siglec-1 is necessary to induce antigen presentation through extracellular vesicle uptake. We postulate that lack of Siglec-1 delays the onset of protective immunity against Mtb by limiting antigen exchange via extracellular vesicles, allowing for an early local spread of mycobacteria that increases the risk for extrapulmonary dissemination. Overall, through this thesis we have explored the concept of antagonistic pleiotropy in co-infected individuals harboring the SIGLEC1 null variant, where the impaired immune control of Mtb in the absence of Siglec-1 could influence the clinical course of HIV-1 infected individuals, thus masking the expected benefits of this variant on delaying AIDS progression.
Universitat Autònoma de Barcelona. Programa de Doctorat en Bioquímica, Biologia Molecular i Biomedicina
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Thiel, Bonnie Arlene. "Bioinformatics approaches to studying immune processes associated with immunity to Mycobacterium tuberculosis infection in the lung and blood." Case Western Reserve University School of Graduate Studies / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=case1627247387242562.
Повний текст джерела
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Kativhu, Chido L. "PhoP-regulated genes contribute to Mycobacteria tuberculosis-induced burst size necrosis in macrophages." eScholarship@UMMS, 2021. https://escholarship.umassmed.edu/gsbs_diss/1120.
Повний текст джерелаАнотація:
Tuberculosis (TB) is primarily a pulmonary disease caused by Mycobacterium tuberculosis (Mtb). Mtb is highly infectious, but studies have shown that only 5–15% of Mtb-infected individuals develop TB disease. The Bacille Calmette-Gu.rin (BCG) vaccine is the only commercially available Mtb vaccine, but its efficacy varies based on the strain used. The Mtb PhoPR-mutant variant, MTBVAC, has been tested as a possible attenuated live vaccine against Mtb. Although it has successfully conferred durable CD4+ T-cell responses in infants, it has also resulted in adverse effects. Our goal is to identify PhoPR-regulated gene(s) that mediate Mtb-induced burst size necrosis in infected cells. PhoPR is a two-component system in mycobacteria. PhoR responds to environmental cues, such as changes in pH, and phosphorylates the PhoP transcription factor, which then activates or suppresses the expression of approximately 40 Mtb genes. The Mtb PhoPR-mutant strain is able to replicate in infected macrophages, but it does not induce the horizontal spread of Mtb to other immune cells. Our lab has previously shown that virulent, cytopathic strains of Mtb, such as H37Rv, suppress early apoptosis, have faster replication rates in macrophages, and trigger cell death at a lethal load threshold of approximately 25 bacteria. Cell death of infected macrophages primarily occurs via necrosis, which involves nuclear pyknosis without DNA fragmentation and general disruption of lipid bilayer membranes. Viable bacilli are released to infect other macrophages and neutrophils recruited to the developing TB lesion. Here, we show that PhoP contributes to burst size necrosis in macrophages and that the PhoP-regulated genes, fadD21 and pks3, are potential drivers of this necrosis. FadD21 and pks3 are involved in the generation of diacyl trehalose/penta-acyl trehalose (DAT/PAT) for cell wall synthesis, suggesting that Mtb cell wall composition may determine virulence. Therefore, we have uncovered potential targets for early intervention or vaccinations to avoid granuloma formation or tissue damage in response to Mtb-induced macrophage necrosis.
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Hartman, Michelle L. "M.tb Killing by Macrophage Innate Immune Mechanisms: A Dissertation." eScholarship@UMMS, 2011. https://escholarship.umassmed.edu/gsbs_diss/606.
Повний текст джерелаАнотація:
Macrophages infected with a heavy burden of M.tb Erdman undergo a cell death that initially resembles apoptosis but quickly transitions to necrosis. Unlike the previously reported TNF dependent apoptosis induced by avirulent Mycobacterium [1], this form of macrophage cell death is not microbicidal [2]. Microbicidal effects are observed however, when the heavily infected macrophage encounters an uninfected naïve macrophage. My studies describe in part, the crosstalk between the uninfected and infected macrophage that results in the killing of the intracellular M.tb Cell contact between the two cell populations is not necessary for this killing of bacilli to occur and the soluble “signal” of communication between the two cell populations is transferrable, without naïve macrophages present, to newly infected cells also resulting in the reduced viability of the bacilli. We have found that when the IL-1 receptor is absent in the naïve macrophage population that the co-culture antimycobacterial effect is abrogated, suggesting that IL-1 released by the infected dying macrophage is critical for naïve macrophages to respond in a way that results in the decrease in mycobacterial viability. The signaling between the two cell population ultimately converges on activation of iNOS in the infected cell however ROS appears not to be involved.
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vanzolini, tania. "Development of new biological drugs for the treatment of fungal infections." Doctoral thesis, Urbino, 2021. http://hdl.handle.net/11576/2692691.
Повний текст джерела
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Iqbal, Salma. "Phenotypical and Functional Characterization of Polarized Human Macrophages." Thesis, Université d'Ottawa / University of Ottawa, 2015. http://hdl.handle.net/10393/32009.
Повний текст джерелаАнотація:
Macrophages can be polarized into M1 and M2 macrophages based on the composition of the milieu. Human macrophages have been poorly characterized. In this study, various macrophage subsets were generated by treating monocyte-derived macrophages (MDMs) with IFNγ (M1), IL-4 (M2a), LPS and IL-1β (M2b) or IL-10 (M2c) which were characterized with respect to their cell surface marker profile and functional profile in the context of cytokine production, susceptibility to HIV infection and apoptosis. Each polarization state demonstrated a unique cell surface marker profile and cytokine profile. In addition M1 macrophages were shown to produce IFNγ post TLR stimulation. Moreover, M1 macrophages were highly sensitive to apoptosis following Smac mimetic treatment. Furthermore, M2a and M2c macrophages were resistant to apoptosis, induced by PI3K blockage and IAPs degradation respectively, and at the same time supported productive HIV infection unlike the other macrophage subsets. These findings might lead to better understanding of HIV reservoir formation and be used to develop therapies to eradicate it.
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Le, Run Eva. "Nouvelles combinaisons de β-lactamines et inhibiteurs de β-lactamase : vers un nouveau traitement des infections à Mycobacterium abscessus chez les patients atteints de mucoviscidose". Electronic Thesis or Diss., Sorbonne université, 2019. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2019SORUS640.pdf.
Повний текст джерелаАнотація:
Mycobacterium abscessus, une mycobactérie à croissance rapide, est responsable d'infections pulmonaires chez les patients atteints de mucoviscidose. Le traitement recommandé comprend une phase initiale basée sur l'association d'un carbapénème (imipénème), d'un macrolide (azithromycine), d'un aminoside (amikacine) et d'une glycylcycline (tigécycline). L’équipe a étudié l’optimisation des traitements impliquant les β-lactamines et a démontré que l’avibactam, un inhibiteur de β-lactamases de 2ème génération appartenant à la famille du diazabicyclooctane, inhibe le β-lactamase BlaMab produit par M. abscessus et augmente de manière significative l’efficacité de l'imipénème à la fois in vitro, dans les macrophages et dans le modèle de poisson zèbre. L'expression du gène de la β-lactamase s'est avérée être induite dans les macrophages infectés. L'objectif du projet de thèse était d'évaluer l'efficacité de nouvelles combinaisons comprenant des d'inhibiteurs de β-lactamase et d'étudier la régulation de la β-lactamase dans les macrophages. Dans la première partie de la thèse, de nouvelles combinaisons d'antibiotiques ont été évaluées in vitro et dans des macrophages infectés par M. abscessus. La rifabutine, habituellement utilisée dans le traitement d'infections dues à d'autres mycobactéries, a montré une activité synergique avec l'imipénème in vitro, mais l'association n'était pas bactéricide. Dans les macrophages infectés, la rifabutine a renforcé l'activité de l'imipénème et l'ajout d'avibactam a entraîné une diminution du nombre de bactérie intracellulaire. Le tédizolide, développé pour le traitement des infections à staphylocoques, a montré une faible synergie in vitro mais pas d’activité bactéricide contre M. abscessus. Dans les macrophages, le tédizolide augmentait l'activité de l'imipénème et la quadruple combinaison imipénème-tédizolide-rifabutine-avibactam permettait de diminuer le nombre de bactéries intracellulaires de 91%. Enfin, l'association de l'imipénème avec le relebactam, un nouvel inhibiteur de β-lactamases développé en association avec l'imipénème, s'est révélée aussi active que la combinaison imipénème-avibactam à la fois in vitro et dans les macrophages. La deuxième partie de la thèse était focalisée sur l'identification du stress responsable de l'induction de la production de β-lactamase dans les macrophages. Dans ce but, M. abscessus a été cultivée in vitro dans différents milieux de culture mimant des conditions de stress aux quelles la bactérie est potentiellement confrontée dans les macrophages. L'activité spécifique de la β-lactamase a été déterminée en utilisant comme substrat une β-lactamine chromogène, la nitrocéfine. Aucune des conditions physicochimiques testées n'a conduit à une induction, incluant un pH acide, de fortes concentrations de métaux, un stress oxydatif ou la présence de β-lactamines. Le dernier objectif était d’étudier l’impact du polymorphisme N versus G situé dans le motif conservé SDN des β-lactamases sur l’activité des combinaisons comprenant une β-lactamine et un inhibiteur de β-lactamase. BlaMab de M. abscessus contient le motif SDN alors que BlaC de M. tuberculosis contient le motif SDG, un polymorphisme qui détermine l'efficacité de l'inhibition de BlaMab par l'avibactam de BlaC par le clavulanate in vitro. Deux souches isogéniques de M. abscessus ont été construites par échange allélique. Comparativement à la souche sauvage, la souche produisant BlaMab avec la substitution N vers G était moins sensible aux combinaisons comprenant l’avibactam avec, en parallèle, un gain d’efficacité pour les combinaisons comprenant le clavulanate. Dans le contexte de BlaC, la substitution de G vers N a potentialisé l'inhibition par l'avibactam. Ces résultats établissent que le polymorphisme SDN/SDG détermine en partie l'efficacité des β-lactamines associées à l'avibactam ou au clavulanate, en accord avec les études cinétiques précédemment réalisées in vitro avec des β-lactamases purifiéesMycobacterium abscessus, a rapidly growing mycobacteria, is responsible for pulmonary infections in cystic fibrosis patients. The recommended treatment consists in an initial phase with the combination of a carbapenem (imipenem), a macrolide (azithromycin), an aminoglycoside (amikacin), and a glycylcycline (tigecycline). The team has investigated the optimization of treatments involving β-lactams and have demonstrated that avibactam, a 2nd generation β-lactamase inhibitor belonging to the diazabicyclooctane (DBO) family, inhibits the β-lactamase BlaMab produced by M. abscessus and substantially increases the efficacy of imipenem both in vitro, intracellularly, and in a zebrafish model. Expression of the β-lactamase gene was found to be induced in infected macrophages. The aim of my PhD project was to evaluate the efficacy of new β-lactam-β-lactamase inhibitor combinations and to investigate β-lactamase regulation in macrophages. In the first part of the thesis, new antibiotic combinations were evaluated in vitro and in macrophages infected by M. abscessus. Rifabutin, usually used in the treatment of infections due to other mycobacteria, showed synergistic activity with imipenem in vitro but the combination was not bactericidal. In infected macrophages, rifabutin enhanced the activity of imipenem and the addition of avibactam led to increased killing. Tedizolid, developed for the treatment of staphylococcal infections, displayed weak synergy in vitro but no bactericidal activity against M. abscessus. In macrophages, tedizolid enhanced the activity of imipenem and the imipenem-tedizolid-rifabutin-avibactam quadruple combination afforded 91% intracellular killing. Finally, the association of imipenem with relebactam, a new β-lactamase inhibitor developed in combination with imipenem, was found to be as active as the imipenem-avibactam both in vitro and in macrophage model. The second part of the thesis was focused on the identification of the stressor triggering the induction of β-lactamase production in macrophages. M. abscessus was grown in vitro in different culture media mimicking stress conditions thought to prevail in macrophages. The β-lactamase specific activity was determined using a chromogenic β-lactam (nitrocefin) as the substrate. None of the physicochemical conditions that were tested led to induction, including acidic pH, high concentrations of metals, oxidative stress or β-lactams. The last objective was to study the impact of the N versus G polymorphism located in the conserved SDN motif of mycobacterial β-lactamases on activity of β-lactam-β-lactamase inhibitor combinations. BlaMab from M. abscessus contains motif SDN whereas BlaC from M. tuberculosis contains motif SDG, a polymorphism that determines efficacious inhibition by either avibactam of clavulanate, respectively. Two isogenic strains of M. abscessus were constructed by allelic exchange. In comparison to the wild-type enzyme, the strain producing BlaMab with the N to G substitution was less susceptible to the β-lactam-avibactam combinations but more efficaciously inhibited by combinations comprising clavulanate. In the context of BlaC, the G to N substitution potentiated inhibition by avibactam. These results establish that the SDN/SDG polymorphism determines the efficacy of combinations comprising a β-lactam and avibactam or clavulanate, as expected from previous kinetic studies performed with purified β-lactamases. N to G and G to N substitutions might be mechanisms of resistance acquisition in M. abscessus and M. tuberculosis, respectively
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Chakraborti, Srinjoy. "Therapeutic Antibody Against Neisseria gonorrhoeae Lipooligosaccharide, a Phase-variable Virulence Factor." eScholarship@UMMS, 2017. https://escholarship.umassmed.edu/gsbs_diss/905.
Повний текст джерелаАнотація:
Neisseria gonorrhoeae (Ng) which causes gonorrhea has become multidrug-resistant, necessitating the development of novel therapeutics and vaccines. mAb 2C7 which targets an epitope within an important virulence factor, the lipooligosaccharide (LOS), is a candidate therapeutic mAb. Ninety-four percent of clinical isolates express the 2C7-epitope which is also a vaccine target.
Ng expresses multiple LOS(s) due to phase-variation (pv) of LOS glycosyltransferase (lgt) genes. mAb 2C7 reactivity requires a lactose extension from the LOS core Heptose (Hep) II (i.e. lgtG ‘ON’ [G+]). Pv results in HepI with: two (2-), three (3-), four (4-), or five (5-) hexoses (Hex). How HepI glycans impact Ng infectivity and mAb 2C7 function are unknown and form the bases of this dissertation.
Using isogenic mutants, I demonstrate that HepI LOS glycans modulate mAb 2C7 binding. mAb 2C7 causes complement (C’)-dependent bacteriolysis of three (2-Hex/G+, 4-Hex/G+, and 5-Hex/G+) of the HepI mutants in vitro. The 3-Hex/G+ mutant (resistant to C’-dependent bacteriolysis) is killed by neutrophils in the presence of mAb and C’. In mice, 2- and 3-Hex/G+ infections are significantly shorter than 4- and 5-Hex/G+ infections. A chimeric mAb 2C7 that hyperactivates C’, attenuates only 4- and 5-Hex/G+ infections.
This study enhances understanding of the role of HepI LOS pv in gonococcal infections and shows that longer HepI glycans are necessary for prolonged infections in vivo. This is the first study that predicts in vitro efficacy of mAb 2C7 against all four targetable HepI glycans thereby strengthening the rationale for development of 2C7-epitope based vaccines and therapeutics.
Книги з теми "Mtb Infection"
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Matthews, Philippa C. Infections caused by mycobacteria. Edited by Philippa C. Matthews. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780198737773.003.0003.
Повний текст джерелаАнотація:
This chapter consists of short notes, diagrams, and tables to summarize infections caused by Mycobacterium tuberculosis (MTB) complex and Mycobacterium leprae. For ease of reference, each topic is broken down into sections, including classification, epidemiology, microbiology, pathophysiology, clinical syndromes, diagnosis, treatment, and prevention.
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Isaacs, John D., and Philip M. Brown. Rituximab and abatacept. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199642489.003.0083.
Повний текст джерелаАнотація:
Two biologics that target cells have been licensed to treat rheumatoid arthritis (RA). Rituximab is a chimeric monoclonal antibody (mAb) against CD20 that depletes B cells; abatacept is a soluble form of CTLA-4 that blocks costimulation and interferes with T-cell function. Both drugs alleviate signs and symptoms of RA and have been shown to retard radiographic progression. Rituximab is licensed for use following failure of tumour necrosis factor (TNF) blockade whereas abatacept's licence permits it use as a first-line biologic. In the United Kingdom, however, the National Institute for Health and Clinical Excellence (NICE) restricts the use of abatacept to patients who develop adverse effects with rituximab or in whom rituximab is contraindicated. As with other biologics, the use of either drug is associated with an enhanced risk of serious infections; additionally, rituximab in particular can cause infusion reactions, requiring prophylaxis. By targeting cells that are central to RA pathogenesis, these drugs provide important additional therapeutic options for patients with RA.
Частини книг з теми "Mtb Infection"
1
Li, Huoming, and Hao Li. "Animal Models of Tuberculosis." In Vaccines for Neglected Pathogens: Strategies, Achievements and Challenges, 139–70. Cham: Springer International Publishing, 2023. http://dx.doi.org/10.1007/978-3-031-24355-4_7.
Повний текст джерелаАнотація:
AbstractTuberculosis (TB) is an important zoonotic disease caused by infection with Mycobacterium tuberculosis (Mtb) complex and has a significant impact on public health. Animal models are suitable tools to mimic the clinical symptoms observed in human TB and provide an opportunity to understand immune responses to infection and the pathophysiology and pathogenesis of TB. In this chapter, we summarize the animal models that are used in Mtb research, including common models such as the mouse, rat, guinea pig, non-human primates, rabbit, cattle and zebrafish, as well as discuss some newly established animal models.
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Garhyan, Jaishree, Bikul Das, and Rakesh Bhatnagar. "Mesenchymal Stem Cells: A Hidden Arsenal for Mtb Persistence, Resuscitation, and Reactivation." In Mycobacterium Tuberculosis: Molecular Infection Biology, Pathogenesis, Diagnostics and New Interventions, 301–14. Singapore: Springer Singapore, 2019. http://dx.doi.org/10.1007/978-981-32-9413-4_17.
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Peralta Alvarez, Marco Polo, Julia L. Marshall, and Rachel Tanner. "Correlates of Protection from Tuberculosis." In Vaccines for Neglected Pathogens: Strategies, Achievements and Challenges, 99–137. Cham: Springer International Publishing, 2023. http://dx.doi.org/10.1007/978-3-031-24355-4_6.
Повний текст джерелаАнотація:
AbstractMultiple immunological mechanisms interact to protect against Mycobacterium tuberculosis (M.tb) infection and/or tuberculosis (TB) disease. However, development of a much-needed new and effective TB vaccine is hindered by the lack of validated correlates of protection. The identification of correlates of protection would facilitate the rational design, optimisation and evaluation of TB vaccine candidates. In this chapter, we discuss what is currently known about protective immunity against M.tb and potential correlates of protection that have been proposed to date, both including and also looking beyond the central role of IFN-γ producing CD4+ T cells to consider innate and humoral immune parameters. Approaches to identifying and validating correlates of protection will also be reviewed.
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Singh, Yadvir. "Comparative In Silico Analyses Reveal Crucial Factors for Virulence, Antigenicity, and Evolution in M.tb." In Mycobacterium Tuberculosis: Molecular Infection Biology, Pathogenesis, Diagnostics and New Interventions, 171–88. Singapore: Springer Singapore, 2019. http://dx.doi.org/10.1007/978-981-32-9413-4_10.
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Kumar Barik, Sushanta, and Jyotirmayee Turuk. "Role of Exosomes in Tuberculosis: Looking Towards a Future Road Map." In Exosomes - Recent Advances From Bench to Bedside [Working Title]. IntechOpen, 2023. http://dx.doi.org/10.5772/intechopen.111544.
Повний текст джерелаАнотація:
Exosomes are generated by the multivesicular degradation of plasma membrane fusion, lysosomal, and extracellular release of intracellular vesicles. The exosome ranges from 30 to 150 nm in size. Exosomes are “bioactive vesicles” that promote intercellular communication. Exosomes contain a variety of biologically active substances packaged with proteins, lipids, and nucleic acids. After any microbe infection into the exosomes, the content of the exosomes changes and is released into the bloodstream. Such type of exosome content could be useful for basic research on exosome biology. Tuberculosis (TB) is a serious infectious disease caused by Mycobacterium tuberculosis (Mtb). During the Mtb infection, the exosomes played an important role in the body’s infection and immune response by releasing several exosome components providing new ideas for diagnosis, prevention, and therapeutic treatment of Mtb infection. The detection of the low abundance of the Mtb numbers or secreted peptides in the serum of TB patients is not possible. The best way of findings for diagnosis and treatment of TB could be possible by the exploration of exosome content analysis through various useful technologies. The study and analysis of exosome content would produce a road map for the future early diagnosis, prognosis estimation, efficacy monitoring, research, and application for TB.
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Bartlett, John G., Robert R. Redfield, and Paul A. Pham. "Prevention of HIV and Prevention of Infection in PLWH." In Bartlett's Medical Management of HIV Infection, 107–74. Oxford University Press, 2019. http://dx.doi.org/10.1093/med/9780190924775.003.0003.
Повний текст джерелаАнотація:
This chapter is about the prevention of HIV and the prevention of opportunistic infections in people living with HIV/AIDs (PLWH). It covers treatment as prevention (TasP), HIV pre-exposure prophylaxis (PrEP) (including indications, initial assessment, and contraindications to PrEP), HIV post-exposure prophylaxis (PEP) (including estimating risk of transmission, timing of PEP initiation, counseling at time of PEP evaluation, and overlap of PEP and PrEP), Mycobacterium tuberculosis (MTB), infections due to bacteria, Treponema pallidum (syphilis), infections due to viruses, human papilloma virus (HPV), influenza A and B, JC polyomavirus (JCV), cryptosporidiosis, mycobacterium avium complex infection, and Pneumocystis jiroveci (formerly Pneumocystis carinii) pneumonia.
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Chen, Bor-Sen. "Genetic-and-epigenetic host/pathogen networks for cross-talk mechanisms in human macrophages and dendritic cells during Mtb infection." In Systems Immunology and Infection Microbiology, 339–74. Elsevier, 2021. http://dx.doi.org/10.1016/b978-0-12-816983-4.00010-9.
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Tiberi, Simon. "Tuberculosis and Other Mycobacterial Infections." In Tutorial Topics in Infection for the Combined Infection Training Programme. Oxford University Press, 2019. http://dx.doi.org/10.1093/oso/9780198801740.003.0035.
Повний текст джерелаАнотація:
Mycobacterium tuberculosis (MTB) is a thin, aerobic, non-spore forming, slow-growing (doubling time twelve hours) non-motile rod-shaped bacteria, belonging to the family Mycobacteriaceae. Mycobacterium tuberculosis complex is made up of several species, including M. tuberculosis, M. bovis, Bacillus Calmette-Guerin (BCG), M. africanum, M. canetii, M.caprae, M. microti, and others. Transmission is via inhalation of aerosolized respiratory secretions. After inhalation, majority of bacilli are captured in the upper respiratory tract by mucus and removed through a process called clearance, although bacteria in small droplets can reach the alveoli where the bacilli are ingested by macrophages. If clearance is not effective infection may result. With the involvement of CD4 lymphocytes, interferon-γ and tumour necrosis factor-α, a granuloma is formed, and bacilli may be destroyed. In many cases, the bacilli are not destroyed and can spread into lymphatics or via blood to other sites (any organs) where it can lie dormant for years. This asymptomatic situation is called latent TB infection (LTBI). It may reactivate in 10% of people throughout their lifetime; this increases with immunosuppression and HIV infection. The course of illness is chronic and indolent. However, rapid progression to fulminant disease may result if the host is immunocompromised. Pulmonary TB is the most common and important form of TB because it is the infectious form of the disease. In areas where reactivation predominates (like the UK), there is a higher proportion of extrapulmonary TB. Tuberculosis bacilli resist destaining with acid alcohol treatment hence the term. This retention is due to complexing of the carbolfuschin Ziehl-Neelsen stain with mycolic acids present in the waxy cell wall, including lipoarabinomannan (which facilitates survival in macrophages). Microscopy will diagnose TB in 80% of smear-positive patients with a first sputum sample, a further 15% with the second, and 5% with a third. In endemic areas finding acid-fast bacilli in sputum has a 98% specificity, but this is not the case in the UK, a low-prevalence setting, where atypical mycobacteria can have a similar prevalence. In the best settings only 60% of culture-positive patients are also sputum smear-positive as liquid culture, the gold standard, and most sensitive test.
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Dian Novita, Bernadette, Ari Christy Mulyono, and Ferdinand Erwin. "Metformin for Tuberculosis Infection." In Metformin - Pharmacology and Drug Interactions. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.99794.
Повний текст джерелаАнотація:
Tuberculosis, caused by Mycobacterium tuberculosis (M.tb), remains the biggest infection burden in the word. Rifampin (RIF) and Isoniazid (INH) are the most effective antibiotics for killing M.tb. However, the resistance rate of rifampin and INH are high and lead to almost 35% treatment failure. Metformin enhanced anti tuberculosis efficacy in killing M. tuberculosis through several mechanism, firstly through autophagia mechanism and secondly by activating superoxide dismutase (SOD). Metformin activated mTOR and AMPK then induced more effective autophagy against M.tb. Superoxide Dismutase (SOD) is an enzyme produced in the host’s antioxidant defense system. SOD neutralizes reactive oxygen species (ROS) that excessively produced during phagocytosis process against M.tb. Excessive production of ROS associated with Th1 overactivation and leads into macrophage activity inhibition and excessive tissue damage. Metformin has ability in improving SOD level during inflammation.
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Kaewphinit, Thongchai, Somchai Santiwatanakul, and Kosum Chansiri. "The Detection of Tuberculosis by Loop-Mediated Isothermal Amplification (LAMP) Combined with a Lateral Flow Dipstick." In Handbook of Research on Diverse Applications of Nanotechnology in Biomedicine, Chemistry, and Engineering, 269–300. IGI Global, 2015. http://dx.doi.org/10.4018/978-1-4666-6363-3.ch013.
Повний текст джерелаАнотація:
Tuberculosis (TB) is an airborne infectious disease caused by the bacterium Mycobacterium Tuberculosis (MTB) and is a persistent problem in developing countries. Present methods for its detection include normal or nested Polymerase Chain Reaction (PCR) followed by electrophoresis, real-time PCR, Ziehl-Neelsen staining, and culture assay. These techniques entail various disadvantages such as high cost, long assay time and use of toxic substances. Novel loop-mediated isothermal amplification (LAMP) permits DNA to be amplified rapidly under constant temperature. The combination of LAMP and chromatographic Lateral Flow Dipstick (LAMP-LFD) by using biotinylated LAMP amplicon hybridized with Fluorescein Isothiocyanate (FITC)-labeled probes are allowed to detect MTB without electrophoresis and interpreted within 3-5 min. LAMP-LFD is as highly sensitive as PCR-electrophoresis method. Based on its sensitivity, specificity, rapidity, cost effectiveness, ease of use, and convenience, LAMP-LFD could be suitable for use in early MTB detection.
Тези доповідей конференцій з теми "Mtb Infection"
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Todorova, Yana, Radoslava Emilova, Vladimir Milanov, Elizabeta Bachiyska, Yuliana Atanasova, Ana Baykova, and Maria Nikolova. "Associations between lipid mediators and cytokine production at different stages of MTB infection." In ERS International Congress 2021 abstracts. European Respiratory Society, 2021. http://dx.doi.org/10.1183/13993003.congress-2021.pa2463.
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Silva, Jallysson Santos, CAIO ARAUJO DA CUNHA, DENNIS MIGUEL LEMOS DA SILVA, and STEFAN VILGES DE OLIVEIRA. "ANÁLISE EPIDEMIOLÓGICA E PROPOSTA DE INTERVENÇÃO PARA OS CASOS DE TUBERCULOSE EM UBERLÂNDIA-MG." In I Congresso Brasileiro de Estudos Epidemiológicos On-line. Revista Multidisciplinar em Saúde, 2022. http://dx.doi.org/10.51161/epidemion/7130.
Повний текст джерелаАнотація:
Introdução: A tuberculose é uma doença infecciosa de notificação compulsória causada pelo agente Mycobacterium tuberculosis. Alguns grupos são mais vulneráveis ao desenvolvimento da doença, como pessoas que vivem com HIV/AIDS, pessoas privadas de liberdade e população em situação de rua. Objetivo: O objetivo do artigo é descrever os casos de Tuberculose ocorridos em Uberlândia, Minas Gerais, entre 2010 e 2019, associando-os a contextos de vulnerabilidade em saúde e discutir propostas de intervenção. Métodos: Estudo epidemiológico descritivo, com análise de dados disponibilizados pelo SINAN/DATASUS sobre os casos notificados de tuberculose entre 2010 e 2019 em Uberlândia, Minas Gerais. Para embasar as propostas de intervenções, foi realizada uma revisão sistemática na base de dados MEDLINE®, utilizando os termos “Epidemiology”, “Infection”, “Mycobacterium tuberculosis” e “Brazilian ou Brasil", com período de busca entre 2010 e 2021. Resultados: Foram notificados 991 casos de tuberculose na cidade de Uberlândia-MG entre 2010 e 2019, com a maior taxa de incidência ocorrendo em 2019, sendo de 20,97/100 mil habitantes. A maioria dos indivíduos infectados foram do sexo masculino, especialmente entre 20 e 39 anos, representando 36,53% do total. No geral, dos 991 casos notificados, 179 apresentavam infecção conjunta com HIV, 44 ocorreram em pessoas em situação de rua e 94 em pessoas privadas de liberdade. Em relação à apresentação, 74,9% dos casos foram notificados de acordo com a forma pulmonar da tuberculose. As propostas de intervenção foram embasadas em quatro artigos e pautadas na utilização do teste Xpert MTB/RIF, treinamento na leitura do Teste Cutâneo para Tuberculose e uso de terapia preventiva. Conclusão: Os dados analisados demonstram que a progressão anual de novos casos é bastante relevante, ainda que apresente uma baixa taxa de incidência por 100 mil habitantes. Por outro lado, os dados sobre populações vulneráveis foram ignorados na coleta de vários casos, indicando que a análise pode estar subestimada.
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Eremeeva, Natalya, Tatyana Tyulkova, Leonid Lavrechuk, Ksenia Belousova, Tatyana Umpeleva, and Diana Vakhrusheva. "Features of development of TB infection caused by different doses of MBT." In ERS International Congress 2018 abstracts. European Respiratory Society, 2018. http://dx.doi.org/10.1183/13993003.congress-2018.pa4732.
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Millman, Alexander J., David Dowdy, Robert Brownell, Adithya Cattamanchi, and John L. Davis. "Cost-Benefit Analysis Of GeneXpert MTB/RIF For Evaluation Of Infectious Tuberculosis At An Urban Public Hospital." In American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California. American Thoracic Society, 2012. http://dx.doi.org/10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a6505.
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Balasaniantc, Goar, Vladimir Galkin, Zinaida Zagdyn, and Peter Yablonskii. "Tuberculosis and HIV infection in combination with multidrug resistant MBT on Northwest of Russia." In ERS International Congress 2016 abstracts. European Respiratory Society, 2016. http://dx.doi.org/10.1183/13993003.congress-2016.pa4262.
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Balasaniantc, Goar. "Bedaquiline in treatment of TB/HIV co-infection patients with extremely-drug resistance of MBT." In ERS International Congress 2018 abstracts. European Respiratory Society, 2018. http://dx.doi.org/10.1183/13993003.congress-2018.pa4742.
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Gosal, Eshrina, Amanda Goodwin, Vidya Navaratnam, Lois Dexter, and Anna L. Rich. "Routine liver function test monitoring of patients treated for active M.TB infection does not influence management: A real-world retrospective study." In ERS International Congress 2018 abstracts. European Respiratory Society, 2018. http://dx.doi.org/10.1183/13993003.congress-2018.pa2684.
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