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Ingrao, Fiona, Fabienne Rauw, Bénédicte Lambrecht, and Thierry van den Berg. "Infectious Bursal Disease: A complex host–pathogen interaction." Developmental & Comparative Immunology 41, no. 3 (November 2013): 429–38. http://dx.doi.org/10.1016/j.dci.2013.03.017.
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Blaustein, Andrew R., Stephanie S. Gervasi, Pieter T. J. Johnson, Jason T. Hoverman, Lisa K. Belden, Paul W. Bradley, and Gisselle Y. Xie. "Ecophysiology meets conservation: understanding the role of disease in amphibian population declines." Philosophical Transactions of the Royal Society B: Biological Sciences 367, no. 1596 (June 19, 2012): 1688–707. http://dx.doi.org/10.1098/rstb.2012.0011.
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Infectious diseases are intimately associated with the dynamics of biodiversity. However, the role that infectious disease plays within ecological communities is complex. The complex effects of infectious disease at the scale of communities and ecosystems are driven by the interaction between host and pathogen. Whether or not a given host–pathogen interaction results in progression from infection to disease is largely dependent on the physiological characteristics of the host within the context of the external environment. Here, we highlight the importance of understanding the outcome of infection and disease in the context of host ecophysiology using amphibians as a model system. Amphibians are ideal for such a discussion because many of their populations are experiencing declines and extinctions, with disease as an important factor implicated in many declines and extinctions. Exposure to pathogens and the host's responses to infection can be influenced by many factors related to physiology such as host life history, immunology, endocrinology, resource acquisition, behaviour and changing climates. In our review, we discuss the relationship between disease and biodiversity. We highlight the dynamics of three amphibian host–pathogen systems that induce different effects on hosts and life stages and illustrate the complexity of amphibian–host–parasite systems. We then review links between environmental stress, endocrine–immune interactions, disease and climate change.
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Thakur, Aneesh, Heidi Mikkelsen, and Gregers Jungersen. "Intracellular Pathogens: Host Immunity and Microbial Persistence Strategies." Journal of Immunology Research 2019 (April 14, 2019): 1–24. http://dx.doi.org/10.1155/2019/1356540.
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Infectious diseases caused by pathogens including viruses, bacteria, fungi, and parasites are ranked as the second leading cause of death worldwide by the World Health Organization. Despite tremendous improvements in global public health since 1950, a number of challenges remain to either prevent or eradicate infectious diseases. Many pathogens can cause acute infections that are effectively cleared by the host immunity, but a subcategory of these pathogens called “intracellular pathogens” can establish persistent and sometimes lifelong infections. Several of these intracellular pathogens manage to evade the host immune monitoring and cause disease by replicating inside the host cells. These pathogens have evolved diverse immune escape strategies and overcome immune responses by residing and multiplying inside host immune cells, primarily macrophages. While these intracellular pathogens that cause persistent infections are phylogenetically diverse and engage in diverse immune evasion and persistence strategies, they share common pathogen type-specific mechanisms during host-pathogen interaction inside host cells. Likewise, the host immune system is also equipped with a diverse range of effector functions to fight against the establishment of pathogen persistence and subsequent host damage. This article provides an overview of the immune effector functions used by the host to counter pathogens and various persistence strategies used by intracellular pathogens to counter host immunity, which enables their extended period of colonization in the host. The improved understanding of persistent intracellular pathogen-derived infections will contribute to develop improved disease diagnostics, therapeutics, and prophylactics.
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Hung, Paul. "Automatic pathogen introduction and removal for live cell imaging of host-pathogen interaction (P3237)." Journal of Immunology 190, no. 1_Supplement (May 1, 2013): 192.4. http://dx.doi.org/10.4049/jimmunol.190.supp.192.4.
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Abstract Host-pathogen interactions represent a significant area of immunology, encompassing the study of how organisms cause infections and diseases. As the field advances, there is increasing interest in using in vitro cell culture models and imaging to study the interactions. However, a few barriers remain with the conventional static cell culture approach. Not only the pathogen will easily outgrow the cells over time, prohibiting further studies, but tedious liquid exchange steps are required to remove excessive pathogens or to add other reagents such as therapeutic compound. To facilitate host-pathogen interaction research with live cell imaging, a microfluidic platform which addresses the problems mentioned above was developed. The platform allows the researchers to culture the cells in a microchamber on a standard inverted microscope, as well as preload up to four different reagents which can be introduced to the cells automatically including the pathogen. The reagent switching function enable the removal of pathogens from the chamber after incision, and subsequent monitoring of host cell response over up to 3 days. The enclosed small volume microchamber also provides practical advantages for working with infectious agents during live cell imaging. An experiment using human intestinal cells infected with engineered E. coli strains was demonstrated. Both an invasive and a non-invasive bacterial strain were monitored for infection with time-lapsed imaging up to 24 hours.
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Savinelli, Stefano, Neil E. Wrigley Kelly, Eoin R. Feeney, Donal B. O'Shea, Andrew E. Hogan, Edgar T. Overton, Alan L. Landay, and Patrick W. Mallon. "Obesity in HIV infection: host-pathogen interaction." AIDS 36, no. 11 (June 21, 2022): 1477–91. http://dx.doi.org/10.1097/qad.0000000000003281.
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Castillo, Christian, and Ulrike Kemmerling. "Host–Pathogen Interaction Involved in Trypanosoma cruzi Infection." Pathogens 11, no. 5 (May 4, 2022): 540. http://dx.doi.org/10.3390/pathogens11050540.
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Henriet, Stefanie S. V., Paul E. Verweij, and Adilia Warris. "Aspergillus nidulans and Chronic Granulomatous Disease: A Unique Host–Pathogen Interaction." Journal of Infectious Diseases 206, no. 7 (July 24, 2012): 1128–37. http://dx.doi.org/10.1093/infdis/jis473.
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Hermann, Corinna. "Review: Variability of host—pathogen interaction." Journal of Endotoxin Research 13, no. 4 (August 2007): 199–218. http://dx.doi.org/10.1177/0968051907082605.
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Bandyopadhyay, Soumyendu Sekhar, Anup Kumar Halder, Sovan Saha, Piyali Chatterjee, Mita Nasipuri, and Subhadip Basu. "Assessment of GO-Based Protein Interaction Affinities in the Large-Scale Human–Coronavirus Family Interactome." Vaccines 11, no. 3 (February 25, 2023): 549. http://dx.doi.org/10.3390/vaccines11030549.
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SARS-CoV-2 is a novel coronavirus that replicates itself via interacting with the host proteins. As a result, identifying virus and host protein-protein interactions could help researchers better understand the virus disease transmission behavior and identify possible COVID-19 drugs. The International Committee on Virus Taxonomy has determined that nCoV is genetically 89% compared to the SARS-CoV epidemic in 2003. This paper focuses on assessing the host–pathogen protein interaction affinity of the coronavirus family, having 44 different variants. In light of these considerations, a GO-semantic scoring function is provided based on Gene Ontology (GO) graphs for determining the binding affinity of any two proteins at the organism level. Based on the availability of the GO annotation of the proteins, 11 viral variants, viz., SARS-CoV-2, SARS, MERS, Bat coronavirus HKU3, Bat coronavirus Rp3/2004, Bat coronavirus HKU5, Murine coronavirus, Bovine coronavirus, Rat coronavirus, Bat coronavirus HKU4, Bat coronavirus 133/2005, are considered from 44 viral variants. The fuzzy scoring function of the entire host–pathogen network has been processed with ~180 million potential interactions generated from 19,281 host proteins and around 242 viral proteins. ~4.5 million potential level one host–pathogen interactions are computed based on the estimated interaction affinity threshold. The resulting host–pathogen interactome is also validated with state-of-the-art experimental networks. The study has also been extended further toward the drug-repurposing study by analyzing the FDA-listed COVID drugs.
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Bogaert, Debby, Paul van der Valk, Reshmi Ramdin, Marcel Sluijter, Evelyn Monninkhof, Ron Hendrix, Ronald de Groot, and Peter W. M. Hermans. "Host-Pathogen Interaction during Pneumococcal Infection in Patients with Chronic Obstructive Pulmonary Disease." Infection and Immunity 72, no. 2 (February 2004): 818–23. http://dx.doi.org/10.1128/iai.72.2.818-823.2004.
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ABSTRACT Acute exacerbation is a frequent complication of chronic obstructive pulmonary disease (COPD). Recent studies suggested a role for bacteria such as Streptococcus pneumoniae in the development of acute exacerbation. For this study, we investigated the following in COPD patients: (i) the epidemiology of pneumococcal colonization and infection, (ii) the effect of pneumococcal colonization on the development of exacerbation, and (iii) the immunological response against S. pneumoniae. We cultured sputa of 269 COPD patients during a stable state and during exacerbation of COPD and characterized 115 pneumococcal isolates by use of serotyping. Moreover, we studied serum immunoglobulin G (IgG) antibody titers, antibody avidities, and functional antibody titers against the seven conjugate vaccine serotypes in these patients. Colonization with only pneumococci (monocultures) increased the risk of exacerbation, with a hazard ratio of 2.93 (95% confidence interval, 1.41 to 6.07). The most prevalent pneumococcal serotypes found were serotypes 19F, 3, 14, 9L/N/V, 23A/B, and 11. We calculated the theoretical coverage for the 7- and 11-valent pneumococcal vaccines to be 60 and 73%, respectively. All patients had detectable IgG levels against the seven conjugate vaccine serotypes. These antibody titers were significantly lower than those in vaccinated healthy adults. Finally, on average, a 2.5-fold rise in serotype-specific and functional antibodies in S. pneumoniae-positive sputum cultures was observed during exacerbation. Our data indicate that pneumococcal colonization in COPD patients is frequently caused by vaccine serotype strains. Moreover, pneumococcal colonization is a risk factor for exacerbation of COPD. Finally, our findings demonstrate that COPD patients are able to mount a significant immune response to pneumococcal infection. COPD patients may therefore benefit from pneumococcal vaccination.
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Boleij, Annemarie, Coby M. Laarakkers, Jolein Gloerich, Dorine W. Swinkels, and Harold Tjalsma. "Surface-Affinity Profiling To Identify Host-Pathogen Interactions." Infection and Immunity 79, no. 12 (September 26, 2011): 4777–83. http://dx.doi.org/10.1128/iai.05572-11.
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ABSTRACTProteolytic treatment of intact bacterial cells has proven to be a convenient approach for the identification of surface-exposed proteins. This class of proteins directly interacts with the outside world, for instance, during adherence to human epithelial cells. Here, we aimed to identify host receptor proteins by introducing a preincubation step in which bacterial cells were first allowed to capture human proteins from epithelial cell lysates. UsingStreptococcus gallolyticusas a model bacterium, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of proteolytically released peptides yielded the identification of a selective number of human epithelial proteins that were retained by the bacterial surface. Of these potential receptors for bacterial interference, (cyto)keratin-8 (CK8) was verified as the most significant hit, and its surface localization was investigated by subcellular fractionation and confocal microscopy. Interestingly, bacterial enolase could be assigned as an interaction partner of CK8 by MS/MS analysis of cross-linked protein complexes and complementary immunoblotting experiments. As surface-exposed enolase has a proposed role in epithelial adherence of several Gram-positive pathogens, its interaction with CK8 seems to point toward a more general virulence mechanism. In conclusion, our study shows that surface-affinity profiling is a valuable tool to identify novel adhesin-receptor pairs, which advocates its application in other hybrid biological systems.
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Tree, Julia A., Helen Flick-Smith, Michael J. Elmore, and Caroline A. Rowland. "The Impact of “Omic” and Imaging Technologies on Assessing the Host Immune Response to Biodefence Agents." Journal of Immunology Research 2014 (2014): 1–17. http://dx.doi.org/10.1155/2014/237043.
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Understanding the interactions between host and pathogen is important for the development and assessment of medical countermeasures to infectious agents, including potential biodefence pathogens such asBacillus anthracis,Ebola virus, andFrancisella tularensis. This review focuses on technological advances which allow this interaction to be studied in much greater detail. Namely, the use of “omic” technologies (next generation sequencing, DNA, and protein microarrays) for dissecting the underlying host response to infection at the molecular level; optical imaging techniques (flow cytometry and fluorescence microscopy) for assessing cellular responses to infection; and biophotonic imaging for visualising the infectious disease process. All of these technologies hold great promise for important breakthroughs in the rational development of vaccines and therapeutics for biodefence agents.
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Baddal, Buket, and Pasquale Marrazzo. "Refining Host-Pathogen Interactions: Organ-on-Chip Side of the Coin." Pathogens 10, no. 2 (February 13, 2021): 203. http://dx.doi.org/10.3390/pathogens10020203.
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Bioinspired organ-level in vitro platforms that recapitulate human organ physiology and organ-specific responses have emerged as effective technologies for infectious disease research, drug discovery, and personalized medicine. A major challenge in tissue engineering for infectious diseases has been the reconstruction of the dynamic 3D microenvironment reflecting the architectural and functional complexity of the human body in order to more accurately model the initiation and progression of host–microbe interactions. By bridging the gap between in vitro experimental models and human pathophysiology and providing alternatives for animal models, organ-on-chip microfluidic devices have so far been implemented in multiple research areas, contributing to major advances in the field. Given the emergence of the recent pandemic, plug-and-play organ chips may hold the key for tackling an unmet clinical need in the development of effective therapeutic strategies. In this review, latest studies harnessing organ-on-chip platforms to unravel host–pathogen interactions are presented to highlight the prospects for the microfluidic technology in infectious diseases research.
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Basset, Christelle, John Holton, Rachel O’Mahony, and Ivan Roitt. "Innate immunity and pathogen–host interaction." Vaccine 21 (June 2003): S12—S23. http://dx.doi.org/10.1016/s0264-410x(03)00195-6.
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Janssen, Riny, Karen A. Krogfelt, Shaun A. Cawthraw, Wilfrid van Pelt, Jaap A. Wagenaar, and Robert J. Owen. "Host-Pathogen Interactions in Campylobacter Infections: the Host Perspective." Clinical Microbiology Reviews 21, no. 3 (July 2008): 505–18. http://dx.doi.org/10.1128/cmr.00055-07.
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SUMMARY Campylobacter is a major cause of acute bacterial diarrhea in humans worldwide. This study was aimed at summarizing the current understanding of host mechanisms involved in the defense against Campylobacter by evaluating data available from three sources: (i) epidemiological observations, (ii) observations of patients, and (iii) experimental observations including observations of animal models and human volunteer studies. Analysis of available data clearly indicates that an effective immune system is crucial for the host defense against Campylobacter infection. Innate, cell-mediated, and humoral immune responses are induced during Campylobacter infection, but the relative importance of these mechanisms in conferring protective immunity against reinfection is unclear. Frequent exposure to Campylobacter does lead to the induction of short-term protection against disease but most probably not against colonization. Recent progress in the development of more suitable animal models for studying Campylobacter infection has opened up possibilities to study the importance of innate and adaptive immunity during infection and in protection against reinfection. In addition, advances in genomics and proteomics technologies will enable more detailed molecular studies. Such studies combined with better integration of host and pathogen research driven by epidemiological findings may truly advance our understanding of Campylobacter infection in humans.
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Yang, Huiying, Yuehua Ke, Jian Wang, Yafang Tan, Sebenzile K. Myeni, Dong Li, Qinghai Shi, et al. "Insight into Bacterial Virulence Mechanisms against Host Immune Response via the Yersinia pestis-Human Protein-Protein Interaction Network." Infection and Immunity 79, no. 11 (September 12, 2011): 4413–24. http://dx.doi.org/10.1128/iai.05622-11.
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ABSTRACTAYersinia pestis-human protein interaction network is reported here to improve our understanding of its pathogenesis. Up to 204 interactions between 66Y. pestisbait proteins and 109 human proteins were identified by yeast two-hybrid assay and then combined with 23 previously published interactions to construct a protein-protein interaction network. Topological analysis of the interaction network revealed that human proteins targeted byY. pestiswere significantly enriched in the proteins that are central in the human protein-protein interaction network. Analysis of this network showed that signaling pathways important for host immune responses were preferentially targeted byY. pestis, including the pathways involved in focal adhesion, regulation of cytoskeleton, leukocyte transendoepithelial migration, and Toll-like receptor (TLR) and mitogen-activated protein kinase (MAPK) signaling. Cellular pathways targeted byY. pestisare highly relevant to its pathogenesis. Interactions with host proteins involved in focal adhesion and cytoskeketon regulation pathways could account for resistance ofY. pestisto phagocytosis. Interference with TLR and MAPK signaling pathways byY. pestisreflects common characteristics of pathogen-host interaction that bacterial pathogens have evolved to evade host innate immune response by interacting with proteins in those signaling pathways. Interestingly, a large portion of human proteins interacting withY. pestis(16/109) also interacted with viral proteins (Epstein-Barr virus [EBV] and hepatitis C virus [HCV]), suggesting that viral and bacterial pathogens attack common cellular functions to facilitate infections. In addition, we identified vasodilator-stimulated phosphoprotein (VASP) as a novel interaction partner of YpkA and showed that YpkA could inhibitin vitroactin assembly mediated by VASP.
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Behera, Manisha, Soma Mondal Ghorai, Sachinandan De, and Hardeep Kaur. "Understanding eco-immunology of bacterial zoonoses and alternative therapeutics toward "One Health"." January-July 7, no. 1 (May 3, 2021): 104–15. http://dx.doi.org/10.14202/ijoh.2021.104-115.
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The current review identifies key bacterial zoonoses, the understanding of comparative immunology, evolutionary trade-offs between emerging bacterial pathogens and their dynamics on both arms of immunity. The several gaps in the literature limit our understanding of spread of prominent bacterial zoonotic diseases and the host-pathogen interactions that may change in response to environmental and social factors. Gaining a more comprehensive understanding of how anthropogenic activities affects the spread of emerging zoonotic diseases, is essential for predicting and mitigating future disease emergence through fine-tuning of surveillance and control measures with respect to different pathogens. This review highlights the urgent need to increase understanding of the comparative immunity of animal reservoirs, design of vaccines according to the homology in host-pathogen interactions, and the alternative strategies to counter the risk of bacterial pathogenic spillover to humans with eventual spread of zoonotic diseases.
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Sarshar, Meysam, Payam Behzadi, Daniela Scribano, Anna Teresa Palamara, and Cecilia Ambrosi. "Acinetobacter baumannii: An Ancient Commensal with Weapons of a Pathogen." Pathogens 10, no. 4 (March 24, 2021): 387. http://dx.doi.org/10.3390/pathogens10040387.
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Acinetobacter baumannii is regarded as a life-threatening pathogen associated with community-acquired and nosocomial infections, mainly pneumonia. The rise in the number of A. baumannii antibiotic-resistant strains reduces effective therapies and increases mortality. Bacterial comparative genomic studies have unraveled the innate and acquired virulence factors of A. baumannii. These virulence factors are involved in antibiotic resistance, environmental persistence, host-pathogen interactions, and immune evasion. Studies on host–pathogen interactions revealed that A. baumannii evolved different mechanisms to adhere to in order to invade host respiratory cells as well as evade the host immune system. In this review, we discuss current data on A. baumannii genetic features and virulence factors. An emphasis is given to the players in host–pathogen interaction in the respiratory tract. In addition, we report recent investigations into host defense systems using in vitro and in vivo models, providing new insights into the innate immune response to A. baumannii infections. Increasing our knowledge of A. baumannii pathogenesis may help the development of novel therapeutic strategies based on anti-adhesive, anti-virulence, and anti-cell to cell signaling pathways drugs.
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Kansal, Rita, David A. Rasko, Jason W. Sahl, George P. Munson, Koushik Roy, Qingwei Luo, Alaullah Sheikh, Kurt J. Kuhne, and James M. Fleckenstein. "Transcriptional Modulation of Enterotoxigenic Escherichia coli Virulence Genes in Response to Epithelial Cell Interactions." Infection and Immunity 81, no. 1 (October 31, 2012): 259–70. http://dx.doi.org/10.1128/iai.00919-12.
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EnterotoxigenicEscherichia coli(ETEC) strains are a leading cause of morbidity and mortality due to diarrheal illness in developing countries. There is currently no effective vaccine against these important pathogens. Because genes modulated by pathogen-host interactions potentially encode putative vaccine targets, we investigated changes in gene expression and surface morphology of ETEC upon interaction with intestinal epithelial cellsin vitro. Pan-genome microarrays, quantitative reverse transcriptase PCR (qRT-PCR), and transcriptional reporter fusions of selected promoters were used to study changes in ETEC transcriptomes. Flow cytometry, immunofluorescence microscopy, and scanning electron microscopy were used to investigate alterations in surface antigen expression and morphology following pathogen-host interactions. Following host cell contact, genes for motility, adhesion, toxin production, immunodominant peptides, and key regulatory molecules, including cyclic AMP (cAMP) receptor protein (CRP) and c-di-GMP, were substantially modulated. These changes were accompanied by visible changes in both ETEC architecture and the expression of surface antigens, including a novel highly conserved adhesin molecule, EaeH. The studies reported here suggest that pathogen-host interactions are finely orchestrated by ETEC and are characterized by coordinated responses involving the sequential deployment of multiple virulence molecules. Elucidation of the molecular details of these interactions could highlight novel strategies for development of vaccines for these important pathogens.
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Nogueira, Sarah Veloso, Alexis A. Smith, Jin-Hong Qin, and Utpal Pal. "A Surface Enolase Participates in Borrelia burgdorferi-Plasminogen Interaction and Contributes to Pathogen Survival within Feeding Ticks." Infection and Immunity 80, no. 1 (October 24, 2011): 82–90. http://dx.doi.org/10.1128/iai.05671-11.
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ABSTRACTBorrelia burgdorferi, a tick-borne bacterial pathogen, causes a disseminated infection involving multiple organs known as Lyme disease. Surface proteins can directly participate in microbial virulence by facilitating pathogen dissemination via interaction with host factors. We show here that a fraction of theB. burgdorferichromosomal gene product BB0337, annotated as enolase or phosphopyruvate dehydratase, is associated with spirochete outer membrane and is surface exposed.B. burgdorferienolase, either in a recombinant form or as a membrane-bound native antigen, displays enzymatic activities intrinsic to the glycolytic pathway. However, the protein also interacts with host plasminogen, potentially leading to its activation and resulting inB. burgdorferi-induced fibrinolysis. As expected, enolase displayed consistent expressionin vivo, however, with a variable temporal and spatial expression during spirochete infection in mice and ticks. Despite an extracellular exposure of the antigen and a potential role in host-pathogen interaction, active immunization of mice with recombinant enolase failed to evoke protective immunity against subsequentB. burgdorferiinfection. In contrast, enolase immunization of murine hosts significantly reduced the acquisition of spirochetes by feeding ticks, suggesting that the protein could have a stage-specific role inB. burgdorferisurvival in the feeding vector. Strategies to interfere with the function of surface enolase could contribute to the development of novel preventive measures to interrupt the spirochete infection cycle and reduce the incidences of Lyme disease.
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Manning, Jessica E., and Tineke Cantaert. "Time to Micromanage the Pathogen-Host-Vector Interface: Considerations for Vaccine Development." Vaccines 7, no. 1 (January 21, 2019): 10. http://dx.doi.org/10.3390/vaccines7010010.
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The current increase in vector-borne disease worldwide necessitates novel approaches to vaccine development targeted to pathogens delivered by blood-feeding arthropod vectors into the host skin. A concept that is gaining traction in recent years is the contribution of the vector or vector-derived components, like salivary proteins, to host-pathogen interactions. Indeed, the triad of vector-host-pathogen interactions in the skin microenvironment can influence host innate and adaptive responses alike, providing an advantage to the pathogen to establish infection. A better understanding of this “bite site” microenvironment, along with how host and vector local microbiomes immunomodulate responses to pathogens, is required for future vaccines for vector-borne diseases. Microneedle administration of such vaccines may more closely mimic vector deposition of pathogen and saliva into the skin with the added benefit of near painless vaccine delivery. Focusing on the ‘micro’–from microenvironments to microbiomes to microneedles–may yield an improved generation of vector-borne disease vaccines in today’s increasingly complex world.
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Wong, Christine E., Subash Sad, and Brian K. Coombes. "Salmonella enterica Serovar Typhimurium Exploits Toll-Like Receptor Signaling during the Host-Pathogen Interaction." Infection and Immunity 77, no. 11 (August 31, 2009): 4750–60. http://dx.doi.org/10.1128/iai.00545-09.
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ABSTRACT Salmonella survives and replicates in host cells by using a type III secretion system to evade host immune defenses. The innate immune system plays an important role as a first line of defense against pathogens and is mediated in part by Toll-like receptors (TLRs); however, the infection dynamics of Salmonella enterica serovar Typhimurium within macrophages stimulated with TLR ligands is poorly understood. We studied the infection dynamics of Salmonella in murine macrophages previously exposed to TLR ligands and report that treatment of macrophages with four different TLR agonists resulted in their increased phagocytic capacity toward Salmonella but not fluorescent microspheres. Further analysis revealed that the intracellular replication of Salmonella was enhanced in TLR-stimulated macrophages in a manner requiring a functional type III secretion system and enhanced transcriptional activity of the sseA virulence gene operon. Studies of mice that normally resolve an acute primary infection with Salmonella revealed that pretreatment of animals with CpG DNA had a detrimental effect on disease outcome. CpG-treated mice infected with Salmonella all succumbed to infection and had higher bacterial loads in the spleen than did control animals. These data suggest that Salmonella can exploit macrophages activated via the innate immune system for increased intracellular survival.
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Vale-Silva, Luís, Françoise Ischer, Salomé Leibundgut-Landmann, and Dominique Sanglard. "Gain-of-Function Mutations inPDR1, a Regulator of Antifungal Drug Resistance in Candida glabrata, Control Adherence to Host Cells." Infection and Immunity 81, no. 5 (March 4, 2013): 1709–20. http://dx.doi.org/10.1128/iai.00074-13.
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ABSTRACTCandida glabratais an emerging opportunistic pathogen that is known to develop resistance to azole drugs due to increased drug efflux. The mechanism consists ofCgPDR1-mediated upregulation of ATP-binding cassette transporters. A range of gain-of-function (GOF) mutations inCgPDR1have been found to lead not only to azole resistance but also to enhanced virulence. This implicatesCgPDR1in the regulation of the interaction ofC. glabratawith the host. To identify specificCgPDR1-regulated steps of the host-pathogen interaction, we investigated in this work the interaction of selectedCgPDR1GOF mutants with murine bone marrow-derived macrophages and human acute monocytic leukemia cell line (THP-1)-derived macrophages, as well as different epithelial cell lines. GOF mutations inCgPDR1did not influence survival and replication within macrophages following phagocytosis but led to decreased adherence to and uptake by macrophages. This may allow evasion from the host's innate cellular immune response. The interaction with epithelial cells revealed an opposite trend, suggesting that GOF mutations inCgPDR1may favor epithelial colonization of the host byC. glabratathrough increased adherence to epithelial cell layers. These data reveal that GOF mutations inCgPDR1modulate the interaction with host cells in ways that may contribute to increased virulence.
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Casadevall, Arturo, and Liise-anne Pirofski. "Host-Pathogen Interactions: Basic Concepts of Microbial Commensalism, Colonization, Infection, and Disease." Infection and Immunity 68, no. 12 (December 1, 2000): 6511–18. http://dx.doi.org/10.1128/iai.68.12.6511-6518.2000.
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Leslie, Jhansi L., Sha Huang, Judith S. Opp, Melinda S. Nagy, Masayuki Kobayashi, Vincent B. Young, and Jason R. Spence. "Persistence and Toxin Production by Clostridium difficile within Human Intestinal Organoids Result in Disruption of Epithelial Paracellular Barrier Function." Infection and Immunity 83, no. 1 (October 13, 2014): 138–45. http://dx.doi.org/10.1128/iai.02561-14.
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Clostridium difficileis the leading cause of infectious nosocomial diarrhea. The pathogenesis ofC. difficileinfection (CDI) results from the interactions between the pathogen, intestinal epithelium, host immune system, and gastrointestinal microbiota. Previous studies of the host-pathogen interaction in CDI have utilized either simple cell monolayers orin vivomodels. While much has been learned by utilizing these approaches, little is known about the direct interaction of the bacterium with a complex host epithelium. Here, we asked if human intestinal organoids (HIOs), which are derived from pluripotent stem cells and demonstrate small intestinal morphology and physiology, could be used to study the pathogenesis of the obligate anaerobeC. difficile. VegetativeC. difficile, microinjected into the lumen of HIOs, persisted in a viable state for up to 12 h. Upon colonization withC. difficileVPI 10463, the HIO epithelium is markedly disrupted, resulting in the loss of paracellular barrier function. Since similar effects were not observed when HIOs were colonized with the nontoxigenicC. difficilestrain F200, we directly tested the role of toxin using TcdA and TcdB purified from VPI 10463. We show that the injection of TcdA replicates the disruption of the epithelial barrier function and structure observed in HIOs colonized with viableC. difficile.
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Swierstra, Jasper, Stephanie Debets, Corné de Vogel, Nicole Lemmens-den Toom, Nelianne Verkaik, Nadjia Ramdani-Bouguessa, Marcel F. Jonkman, et al. "IgG4 Subclass-Specific Responses to Staphylococcus aureus Antigens Shed New Light on Host-Pathogen Interaction." Infection and Immunity 83, no. 2 (November 17, 2014): 492–501. http://dx.doi.org/10.1128/iai.02286-14.
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IgG4 responses are considered indicative for long-term or repeated exposure to particular antigens. Therefore, studying IgG4-specific antibody responses againstStaphylococcus aureusmight generate new insights into the respective host-pathogen interactions and the microbial virulence factors involved. Using a bead-based flow cytometry assay, we determined total IgG (IgGt), IgG1, and IgG4 antibody responses to 40 differentS. aureusvirulence factors in sera from healthy persistent nasal carriers, healthy persistent noncarriers, and patients with various staphylococcal infections from three distinct countries. IgGt responses were detected against all tested antigens. These were mostly IgG1 responses. In contrast, IgG4 antibodies were detected to alpha-toxin, chemotaxis inhibitory protein ofS. aureus(CHIPS), exfoliative toxins A and B (ETA and -B), HlgB, IsdA, LukD, -E, -F, and -S, staphylococcal complement inhibitor (SCIN), staphylococcal enterotoxin C (SEC), staphylococcal superantigen-like proteins 1, 3, 5, and 9 (SSL1, -3, -5, and -9), and toxic shock syndrome toxin 1 (TSST-1) only. Large interpatient variability was observed, and the type of infection or geographical location did not reveal conserved patterns of response. As persistentS. aureuscarriers trended toward IgG4 responses to a larger number of antigens than persistent noncarriers, we also investigated sera from patients with epidermolysis bullosa (EB), a genetic blistering disease associated with highS. aureuscarriage rates. EB patients responded immunologically to significantly more antigens than noncarriers and trended toward even more responses than carriers. Altogether, we conclude that the IgG4 responses against a restricted panel of staphylococcal antigens consisting primarily of immune modulators and particular toxins indicate important roles for these virulence factors in staphylococcal pathogen-host interactions, such as chronicity of colonization and/or (subclinical) infections.
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Shlykova, D. S., V. M. Pisarev, A. M. Gaponov, and A. V. Tutelyan. "Interaction of bacterial extracellular microvesicles with eukaryotic cells." Medical Immunology (Russia) 22, no. 6 (January 10, 2021): 1065–84. http://dx.doi.org/10.15789/1563-0625-iob-2079.
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Bacterial extracellular microvesicles (BMV) are formed by nonpathogenic, pathogenic and opportunistic bacteria. BMV are spherical bilayer-membrane organelles containing different cargoes: lipopolysaccharides, pathogen associated molecular patterns (PUMP), DNA, RNA, signal molecules, proteins, antibiotic resistance factors, virulence factors, toxins providing various immune response options and conducive to the survival and pathogen dissemination in the human body. BMVs secretion play an important role in the ability of microorganisms to cause various diseases. BMV are involved in biofilms formation, help bacteria to obtain nutrition in a nutrient-poor conditions, to evade the host's immune response, provide communication and surviving in a stressful environment during infection inside the host. The heterogeneity of the biogenesis mechanisms causes differences in the BMV and their characteristics including virulence rate. BMVs host cells entering is mediated by several mechanisms and helps to activate innate and adaptive immune reactions. This review focuses on interaction study of BMV with various eukaryotic cells types including neutrophils, dendritic cells, macrophages, epithelial, endothelial cells. This interaction depends on bacteria species, type of target cell and number of vesicles and can lead to different responses: non-immunogenic, pro-inflammatory, cytotoxic. Subcellular and molecular mechanisms related to the involvement of extracellular microvesicles in host's immune response modulation are presented. Stimulation of immune response is provided by increased secretion of proinflammatory cytokines and chemokines. In some cases BMV use mechanisms to evade immune surveillance: anti-inflammatory cytokines secretion, alterations of phagocytosis and chemotaxis of macrophages, increasing the proteolytic cleavage of CD14 on the macrophage surface, alterations of antigen-presenting function of dendritic cells, T-cell proliferation suppression, reducing the pro-inflammatory cytokines secretion, evasion of host-immune cells direct interactions, destruction of neutrophilic traps. These features allow bacterial cells to survive in the human body, increase their invasive potential, and reduce the excessive inflammatory reactions leading to death of the pathogen itself and life-threatening damage of tissues and organs of the host. Further studies of these mechanisms will improve existing therapeutic approaches to the infectious diseases treatment.
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Gómez-Duarte, Oscar G., and Pearay L. Ogra. "Development of Mucosal Immunity: Functional Interactions with Mucosal Microbiome in Health and Disease." Current Immunology Reviews 15, no. 2 (December 18, 2019): 154–65. http://dx.doi.org/10.2174/1573395515666190225153529.
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The mucosal surfaces and the skin are the primary sites of interactions between the mammalian host and the external environment. These sites are exposed continuously to the diverse components of the environment, including subcellular, unicellular and multicellular organisms, dietary agents and food products; and numerous other soluble or cellular air or water borne products. The development of innate and adaptive immunity in the mucosal surfaces and the skin are the principal mechanism of mammalian defense evolved to date, in order to maintain effective homeostatic balance between the host and the external environment. The innate immune functions are mediated by a number of host specific Pathogen Recognition Receptors (PRR), designed to recognize unique Pathogen Associated Molecular Patterns (PAMP), essential to the molecular structure of the microorganism. The major components of specific adaptive immunity in the mucosal surfaces include the organized antigen-reactive lymphoid follicles in different inductive mucosal sites and the effector sites of the lamina propria and sub-epithelial regions, which contain lymphoid and plasma cells, derived by the homing of antigen sensitized cells from the inductive sites. The acquisition of environmental microbiome by the neonate in its mucosal surfaces and the skin, which begins before or immediately after birth, has been shown to play a critical and complex role in the development of mucosal immunity. This report provides an overview of the mammalian microbiome and highlights its role in the evolution and functional development of immunologic defenses in the mucosal surface under normal physiologic conditions and during infectious and non-infectious inflammatory pathologic states associated with altered microbiota.
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El-Etr, Sahar H., Ling Yan, and Jeffrey D. Cirillo. "Fish Monocytes as a Model for Mycobacterial Host-Pathogen Interactions." Infection and Immunity 69, no. 12 (December 1, 2001): 7310–17. http://dx.doi.org/10.1128/iai.69.12.7310-7317.2001.
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ABSTRACT Mycobacterium marinum, a relatively rapid-growing fish and human pathogen, has become an important model for the investigation of mycobacterial pathogenesis. M. marinumis closely related to the Mycobacterium tuberculosiscomplex and causes a disease in fish and amphibians with pathology similar to tuberculosis. We have developed an in vitro model for the study of M. marinum virulence mechanisms using the carp monocytic cell line CLC (carp leukocyte culture). We found that fish monocytes can differentiate between pathogenic and nonpathogenic mycobacterial species. Interestingly, M. marinum enters fish monocytes at a 40- to 60-fold-higher rate thanMycobacterium smegmatis. In addition, M. marinum survives and replicates in fish monocytes whileM. smegmatis is killed. We also found that M. marinum inhibits lysosomal fusion in fish monocytes, indicating that these cells may be used to dissect the mechanisms of intracellular trafficking in mycobacteria. We conclude from these observations that monocytic cells from fish, a natural host for M. marinum, provide an extremely valuable model for the identification and characterization of mycobacterial virulence determinants in the laboratory.
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Ghedira, Kais, Yosr Hamdi, Abir El Béji, and Houcemeddine Othman. "An Integrative Computational Approach for the Prediction of Human-Plasmodium Protein-Protein Interactions." BioMed Research International 2020 (December 19, 2020): 1–11. http://dx.doi.org/10.1155/2020/2082540.
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Host-pathogen molecular cross-talks are critical in determining the pathophysiology of a specific infection. Most of these cross-talks are mediated via protein-protein interactions between the host and the pathogen (HP-PPI). Thus, it is essential to know how some pathogens interact with their hosts to understand the mechanism of infections. Malaria is a life-threatening disease caused by an obligate intracellular parasite belonging to the Plasmodium genus, of which P. falciparum is the most prevalent. Several previous studies predicted human-plasmodium protein-protein interactions using computational methods have demonstrated their utility, accuracy, and efficiency to identify the interacting partners and therefore complementing experimental efforts to characterize host-pathogen interaction networks. To predict potential putative HP-PPIs, we use an integrative computational approach based on the combination of multiple OMICS-based methods including human red blood cells (RBC) and Plasmodium falciparum 3D7 strain expressed proteins, domain-domain based PPI, similarity of gene ontology terms, structure similarity method homology identification, and machine learning prediction. Our results reported a set of 716 protein interactions involving 302 human proteins and 130 Plasmodium proteins. This work provides a list of potential human-Plasmodium interacting proteins. These findings will contribute to better understand the mechanisms underlying the molecular determinism of malaria disease and potentially to identify candidate pharmacological targets.
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Okai, Blessing, Natalie Lyall, Neil A. R. Gow, Judith M. Bain, and Lars-Peter Erwig. "Rab14 Regulates Maturation of Macrophage Phagosomes Containing the Fungal Pathogen Candida albicans and Outcome of the Host-Pathogen Interaction." Infection and Immunity 83, no. 4 (February 2, 2015): 1523–35. http://dx.doi.org/10.1128/iai.02917-14.
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Avoidance of innate immune defense is an important mechanism contributing to the pathogenicity of microorganisms. The fungal pathogenCandida albicansundergoes morphogenetic switching from the yeast to the filamentous hyphal form following phagocytosis by macrophages, facilitating its escape from the phagosome, which can result in host cell lysis. We show that the intracellular host trafficking GTPase Rab14 plays an important role in protecting macrophages from lysis mediated byC. albicanshyphae. Live-cell imaging of macrophages expressing green fluorescent protein (GFP)-tagged Rab14 or dominant negative Rab14, or with small interfering RNA (siRNA)-mediated knockdown of Rab14, revealed the temporal dynamics of this protein and its influence on the maturation of macrophage phagosomes following the engulfment ofC. albicanscells. Phagosomes containing liveC. albicanscells became transiently Rab14 positive within 2 min following engulfment. The duration of Rab14 retention on phagosomes was prolonged for hyphal cargo and was directly proportional to hyphal length. Interference with endogenous Rab14 did not affect the migration of macrophages towardC. albicanscells, the rate of engulfment, the overall uptake of fungal cells, or early phagosome processing. However, Rab14 depletion delayed the acquisition of the late phagosome maturation markers LAMP1 and lysosomal cathepsin, indicating delayed formation of a fully bioactive lysosome. This was associated with a significant increase in the level of macrophage killing byC. albicans. Therefore, Rab14 activity promotes phagosome maturation duringC. albicansinfection but is dysregulated on the phagosome in the presence of the invasive hyphal form, which favors fungal survival and escape.
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Manzer, Haider S., Ricardo I. Villarreal, and Kelly S. Doran. "Targeting the BspC-vimentin interaction to develop anti-virulence therapies during Group B streptococcal meningitis." PLOS Pathogens 18, no. 3 (March 22, 2022): e1010397. http://dx.doi.org/10.1371/journal.ppat.1010397.
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Bacterial infections are a major cause of morbidity and mortality worldwide and the rise of antibiotic resistance necessitates development of alternative treatments. Pathogen adhesins that bind to host cells initiate disease pathogenesis and represent potential therapeutic targets. We have shown previously that the BspC adhesin in Group B Streptococcus (GBS), the leading cause of bacterial neonatal meningitis, interacts with host vimentin to promote attachment to brain endothelium and disease development. Here we determined that the BspC variable (V-) domain contains the vimentin binding site and promotes GBS adherence to brain endothelium. Site directed mutagenesis identified a binding pocket necessary for GBS host cell interaction and development of meningitis. Using a virtual structure-based drug screen we identified compounds that targeted the V-domain binding pocket, which blocked GBS adherence and entry into the brain in vivo. These data indicate the utility of targeting the pathogen-host interface to develop anti-virulence therapeutics.
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Peltz, Gary, Aimee K. Zaas, Ming Zheng, Norma V. Solis, Mason X. Zhang, Hong-Hsing Liu, Yajing Hu, et al. "Next-Generation Computational Genetic Analysis: Multiple Complement Alleles Control Survival after Candida albicans Infection." Infection and Immunity 79, no. 11 (August 29, 2011): 4472–79. http://dx.doi.org/10.1128/iai.05666-11.
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ABSTRACTCandida albicansis a fungal pathogen that causes severe disseminated infections that can be lethal in immunocompromised patients. Genetic factors are known to alter the initial susceptibility to and severity ofC. albicansinfection. We developed a next-generation computational genetic mapping program with advanced features to identify genetic factors affecting survival in a murine genetic model of hematogenousC. albicansinfection. This computational tool was used to analyze the median survival data after inbred mouse strains were infected withC. albicans, which provides a useful experimental model for identification of host susceptibility factors. The computational analysis indicated that genetic variation within early classical complement pathway components (C1q,C1r, andC1s) could affect survival. Consistent with the computational results, serum C1 binding to this pathogen was strongly affected byC1rsalleles, as was survival of chromosome substitution strains. These results led to a combinatorial, conditional genetic model, involving an interaction betweenC5andC1r/salleles, which accurately predicted survival after infection. Beyond applicability to infectious disease, this information could increase our understanding of the genetic factors affecting susceptibility to autoimmune and neurodegenerative diseases.
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NIEDBALSKI, WIESŁAW. "BTV-vector-host interaction: the epidemiological triangle in disease transmission." Medycyna Weterynaryjna 74, no. 1 (2018): 5996–2018. http://dx.doi.org/10.21521/mw.5996.
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Understanding the interaction between the bluetongue virus (BTV), the Culicoides vector and the ruminant host is essential to control bluetongue (BT). This triangle of interaction can be understood individually at the level of the virus, the level of vector and the host level. BTV-vector-host interactions involve physiological and ecological mechanisms, and they have evolved under a specific set of environmental conditions. Recent advances in understanding this interaction include increased knowledge of the virus replication cycle, BTV immunology and pathogenesis in the vertebrate host, as well as the virulence and pathogenicity features of newly discovered BTV serotypes. To understand the virus-host-vector interaction, new molecular biology techniques and experimental infection biology methods have been widely used. The next-generation sequencing, the establishment of a reverse genetics system for the virus, and development of novel infection models and refinement of the existing BTV experimental infection methodologies have proven very helpful. This progress in biotechnology has also made it possible to develop new-generation BTV vaccines, such as disabled infectious single cycle (DISC) vaccines and disabled infectious single animal (DISA) vaccines. However, several questions still need to be answered, such as those concerning cellular pathways involved in the induction of innate immunity and the function of NS4 in the BTV replication cycle. In addition, the identities of specific molecular determinants and the role of quasi-species diversity in determining BTV phenotype are still unclear and should be better explained..
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Plain, Karren M., Kumudika de Silva, John Earl, Douglas J. Begg, Auriol C. Purdie, and Richard J. Whittington. "Indoleamine 2,3-Dioxygenase, Tryptophan Catabolism, and Mycobacterium avium subsp. paratuberculosis: a Model for Chronic Mycobacterial Infections." Infection and Immunity 79, no. 9 (July 5, 2011): 3821–32. http://dx.doi.org/10.1128/iai.05204-11.
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ABSTRACTVirulent mycobacterial infections progress slowly, with a latent period that leads to clinical disease in a proportion of cases.Mycobacterium aviumsubsp.paratuberculosisis an intracellular pathogen that causes paratuberculosis or Johne's disease (JD), a chronic intestinal disease of ruminants. Indoleamine 2,3-dioxygenase (IDO), an enzyme that regulates tryptophan metabolism, was originally reported to have a role in intracellular pathogen killing and has since been shown to have an important immunoregulatory role in chronic immune diseases. Here we demonstrate an association between increased IDO levels and progression to clinical mycobacterial disease in a natural host, characterizing gene expression, protein localization, and functional effects. IDO mRNA levels were significantly increased inM. aviumsubsp.paratuberculosis-infected monocytic cells. Levels of both IDO gene and protein expression were significantly upregulated within the affected tissues of sheep with JD, particularly at the site of primary infection, the ileum, of animals with severe multibacillary disease. Lesion severity was correlated with the level of IDO gene expression. IDO gene expression was also increased in the peripheral blood cells ofM. aviumsubsp.paratuberculosis-exposed sheep and cattle. IDO breaks down tryptophan, and systemic increases were functional, as shown by decreased plasma tryptophan levels, which correlated with the onset of clinical signs, a stage well known to be associated with Th1 immunosuppression. IDO may be involved in downregulating immune responses toM. aviumsubsp.paratuberculosisand other virulent mycobacteria, which may be an example of the pathogen harnessing host immunoregulatory pathways to aid survival. These findings raise new questions about the host-mycobacterium interactions in the progression from latent to clinical disease.
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McHenry, Michael L., Eddie M. Wampande, Moses L. Joloba, LaShaunda L. Malone, Harriet Mayanja-Kizza, William S. Bush, W. Henry Boom, Scott M. Williams, and Catherine M. Stein. "Interaction between M. tuberculosis Lineage and Human Genetic Variants Reveals Novel Pathway Associations with Severity of TB." Pathogens 10, no. 11 (November 15, 2021): 1487. http://dx.doi.org/10.3390/pathogens10111487.
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Tuberculosis (TB) remains a major public health threat globally, especially in sub-Saharan Africa. Both human and Mycobacterium tuberculosis (MTBC) genetic variation affect TB outcomes, but few studies have examined if and how the two genomes interact to affect disease. We hypothesize that long-term coexistence between human genomes and MTBC lineages modulates disease to affect its severity. We examined this hypothesis in our TB household contact study in Kampala, Uganda, in which we identified three MTBC lineages, of which one, L4.6-Uganda, is clearly derived and hence recent. We quantified TB severity using the Bandim TBscore and examined the interaction between MTBC lineage and human single-nucleotide polymorphisms (SNPs) genome-wide, in two independent cohorts of TB cases (n = 149 and n = 127). We found a significant interaction between an SNP in PPIAP2 and the Uganda lineage (combined p = 4 × 10−8). PPIAP2 is a pseudogene that is highly expressed in immune cells. Pathway and eQTL analyses indicated potential roles between coevolving SNPs and cellular replication and metabolism as well as platelet aggregation and coagulation. This finding provides further evidence that host–pathogen interactions affect clinical presentation differently than host and pathogen genetic variation independently, and that human–MTBC coevolution is likely to explain patterns of disease severity.
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Luna, Evelyn. "Finding the balance between protective and pathologic vaccine induced immunity using LCMV specific T lymphocytes." Journal of Immunology 200, no. 1_Supplement (May 1, 2018): 125.20. http://dx.doi.org/10.4049/jimmunol.200.supp.125.20.
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Abstract Vaccination remains one of the most effective strategies for preventing human diseases caused by infectious pathogens, yet developing an efficacious vaccine for persistent viral infections such as HIV remains a difficult aim of much research. Vaccines expressing pathogen T cell epitopes has been a widely employed strategy to try and improve the efficacy of vaccines against chronic viral infections. However, selectively engaging T cells has the potential to increase rather than prevent pathology during subsequent infection, consequently shifting a mild disease to a lethal one. Thus, determining the immune parameters that lead to protection versus those that mediate pathology is critical for developing a safe and effective vaccine against persistent viral infections. Using lymphocytic choriomeningitis virus (LCMV) we investigated how the precursor frequency of CD8 T cells affects the balance of protection vs. pathology during chronic viral infection. We found that the balance is based largely on the number of T cells responding to the pathogen. Intermediate numbers of responding CD8 T cells resulted in maximum pathology. We have also observed that increasing vaccine-induced CD4 T cell responses, unlike CD8 T cells, never leads to protection, but instead high host mortality. We have now began to study the interaction of CD8 and CD4 T cells during infection to determine what effect CD4 T cells have in protective versus pathologic vaccine-induced immunity and what exactly mediates such responses.
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Di Pietrantonio, Tania, José A. Correa, Marianna Orlova, Marcel A. Behr, and Erwin Schurr. "Joint Effects of Host Genetic Background and Mycobacterial Pathogen on Susceptibility to Infection." Infection and Immunity 79, no. 6 (March 14, 2011): 2372–78. http://dx.doi.org/10.1128/iai.00985-10.
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ABSTRACTThe present study examined the differential contribution of host genetic background and mycobacterial pathogen variability to biological and mechanistic phenotypes of infection. For this purpose, A/J and C57BL/6J mice were infected intravenously with a low dose ofMycobacterium tuberculosisH37Rv or the Russia, Japan, and Pasteur substrains ofMycobacterium bovisbacille Calmette-Guérin (BCG). The pulmonary bacterial counts (number of CFU) and transcript levels of select cytokines (e.g.,Ifng,Il12b, andIl4) at 1, 3, and 6 weeks postinfection were measured as biological and mechanistic phenotypes, respectively. The individual and combined impact of the host and mycobacteria on these phenotypes was assessed using three-way analysis of variance (ANOVA), which partitions phenotypic variation into host, pathogen, time, and interaction effects. All phenotypes, except pulmonaryIl4transcript levels, displayed evidence for host-mycobacterium specificity by means of significant interaction terms. Pulmonary expression profiles of 34 chemokines and chemokine-related genes were compared across the hosts and mycobacteria. The differences in induction of these immune messenger genes between A/J and C57BL/6J mice were modest and generally failed to reach significance. In contrast, the mycobacteria induced significant variance in a subset of the immune messenger genes, which was more evident in A/J mice relative to that in C57BL/6J mice. Overall, the results demonstrated the importance of considering the joint effects of the mycobacterial and host genetic backgrounds on susceptibility to mycobacterial infections.
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Ferrando, Maria Laura, Astrid de Greeff, Willemien J. M. van Rooijen, Norbert Stockhofe-Zurwieden, Jens Nielsen, Paul J. Wichgers Schreur, Yvonne Pannekoek, et al. "Host-pathogen Interaction at the Intestinal Mucosa Correlates With Zoonotic Potential of Streptococcus suis." Journal of Infectious Diseases 212, no. 1 (December 18, 2014): 95–105. http://dx.doi.org/10.1093/infdis/jiu813.
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Cilia, Giovanni. "Special Issue: “Infection in Honey Bees: Host–Pathogen Interaction and Spillover”." Pathogens 11, no. 1 (January 8, 2022): 77. http://dx.doi.org/10.3390/pathogens11010077.
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Bannoehr, Jeanette, Nouri L. Ben Zakour, Mark Reglinski, Neil F. Inglis, Sabitha Prabhakaran, Even Fossum, David G. Smith, et al. "Genomic and Surface Proteomic Analysis of the Canine Pathogen Staphylococcus pseudintermedius Reveals Proteins That Mediate Adherence to the Extracellular Matrix." Infection and Immunity 79, no. 8 (May 16, 2011): 3074–86. http://dx.doi.org/10.1128/iai.00137-11.
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ABSTRACTCell wall-associated (CWA) proteins made by Gram-positive pathogens play a fundamental role in pathogenesis.Staphylococcus pseudintermediusis a major animal pathogen responsible for the canine skin disease bacterial pyoderma. Here, we describe the bioinformatic analysis of the family of 18 predicted CWA proteins encoded in the genome ofS. pseudintermediusstrain ED99 and determine their distribution among a phylogenetically diverse panel ofS. pseudintermediusclinical isolates and closely related species of theStaphylococcus intermediusgroup. In parallel, we employed a proteomic approach to identify proteins presented on the surface of strain ED99in vitro, revealing a total of 60 surface-localized proteins in one or more phases of growth, including 6 of the 18 genome-predicted CWA proteins. Based on these analyses, we selected two CWA proteins (SpsD and SpsL) encoded by all strains examined and investigated their capacity to mediate adherence to extracellular matrix proteins. We discovered that SpsD and SpsL mediated binding of a heterologous host,Lactococcus lactis, to fibrinogen and fibronectin and that SpsD mediated binding to cytokeratin 10, a major constituent of mammalian skin. Of note, the interaction with fibrinogen was host-species dependent, suggestive of a role for SpsD and SpsL in the host tropism ofS. pseudintermedius. Finally, we identified IgG specific for SpsD and SpsL in sera from dogs with bacterial pyoderma, implying that both proteins are expressed during infection. The combined genomic and proteomic approach employed in the current study has revealed novel host-pathogen interactions which represent candidate therapeutic targets for the control of bacterial pyoderma.
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Páez, David J., Rachel L. Powers, Peng Jia, Natalia Ballesteros, Gael Kurath, Kerry A. Naish, and Maureen K. Purcell. "Temperature Variation and Host Immunity Regulate Viral Persistence in a Salmonid Host." Pathogens 10, no. 7 (July 7, 2021): 855. http://dx.doi.org/10.3390/pathogens10070855.
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Environmental variation has important effects on host–pathogen interactions, affecting large-scale ecological processes such as the severity and frequency of epidemics. However, less is known about how the environment interacts with host immunity to modulate virus fitness within hosts. Here, we studied the interaction between host immune responses and water temperature on the long-term persistence of a model vertebrate virus, infectious hematopoietic necrosis virus (IHNV) in steelhead trout (Oncorhynchus mykiss). We first used cell culture methods to factor out strong host immune responses, allowing us to test the effect of temperature on viral replication. We found that 15 ∘C water temperature accelerated IHNV replication compared to the colder 10 and 8 ∘C temperatures. We then conducted in vivo experiments to quantify the effect of 6, 10, and 15 ∘C water temperatures on IHNV persistence over 8 months. Fish held at 15 and 10 ∘C were found to have higher prevalence of neutralizing antibodies compared to fish held at 6 ∘C. We found that IHNV persisted for a shorter time at warmer temperatures and resulted in an overall lower fish mortality compared to colder temperatures. These results support the hypothesis that temperature and host immune responses interact to modulate virus persistence within hosts. When immune responses were minimized (i.e., in vitro) virus replication was higher at warmer temperatures. However, with a full potential for host immune responses (i.e., in vivo experiments) longer virus persistence and higher long-term virulence was favored in colder temperatures. We also found that the viral RNA that persisted at later time points (179 and 270 days post-exposure) was mostly localized in the kidney and spleen tissues. These tissues are composed of hematopoietic cells that are favored targets of the virus. By partitioning the effect of temperature on host and pathogen responses, our results help to better understand environmental drivers of host–pathogen interactions within hosts, providing insights into potential host–pathogen responses to climate change.
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Linsuwanon, Piyada, Sirima Wongwairot, Nutthanun Auysawasdi, Taweesak Monkanna, Allen L. Richards, Surachai Leepitakrat, Piyanate Sunyakumthorn, Rawiwan Im-Erbsin, Katie Poole-Smith, and Patrick McCardle. "Establishment of a Rhesus Macaque Model for Scrub Typhus Transmission: Pilot Study to Evaluate the Minimal Orientia tsutsugamushi Transmission Time by Leptotrombidium chiangraiensis Chiggers." Pathogens 10, no. 8 (August 13, 2021): 1028. http://dx.doi.org/10.3390/pathogens10081028.
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Recently, an intradermal inoculation of the rhesus macaque model of scrub typhus has been characterized at our institution. The current project was to establish a rhesus macaque model of scrub typhus using the naturally infected chigger challenge method that faithfully mimics the natural route of pathogen transmission to fully understand the host-pathogen-vector interactions influencing pathogen transmission. Unlike the needle-based inoculation route, Orientia tsutsugamushi-infected chiggers introduce both pathogen and chigger saliva into the host epidermis at the bite site. However, information on the interaction or influence of chigger saliva on pathogenesis and immunity of host has been limited, consequently hindering vaccine development and transmission-blocking studies. To characterize chigger inoculated O. tsutsugamushi in rhesus macaques, we determined the minimum chigger attachment time required to efficiently transmit O. tsutsugamushi to the immunocompetent hosts and preliminary assessed clinical parameters, course of bacterial infection, and host’s immunological response to identifying potential factors influencing pathogen infection. Chigger infestation on hosts resulted in: (i) Rapid transmission of O. tsutsugamushi within 1 h and (ii) antigen-specific type I and II T-cell responses were markedly increased during the acute phase of infection, suggesting that both systems play critical roles in response to the pathogen control during the primary infection. In summary, we demonstrate that O. tsutsugamushi infection in rhesus macaques via chigger challenge recapitulates the time of disease onset and bacteremia observed in scrub typhus patients. Levels of proinflammatory cytokines and chemokines were positively correlated with bacteremia.
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Mara, Kostlend, Meiling Dai, Aaron M. Brice, Marina R. Alexander, Leon Tribolet, Daniel S. Layton, and Andrew G. D. Bean. "Investigating the Interaction between Negative Strand RNA Viruses and Their Hosts for Enhanced Vaccine Development and Production." Vaccines 9, no. 1 (January 17, 2021): 59. http://dx.doi.org/10.3390/vaccines9010059.
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The current pandemic has highlighted the ever-increasing risk of human to human spread of zoonotic pathogens. A number of medically-relevant zoonotic pathogens are negative-strand RNA viruses (NSVs). NSVs are derived from different virus families. Examples like Ebola are known for causing severe symptoms and high mortality rates. Some, like influenza, are known for their ease of person-to-person transmission and lack of pre-existing immunity, enabling rapid spread across many countries around the globe. Containment of outbreaks of NSVs can be difficult owing to their unpredictability and the absence of effective control measures, such as vaccines and antiviral therapeutics. In addition, there remains a lack of essential knowledge of the host–pathogen response that are induced by NSVs, particularly of the immune responses that provide protection. Vaccines are the most effective method for preventing infectious diseases. In fact, in the event of a pandemic, appropriate vaccine design and speed of vaccine supply is the most critical factor in protecting the population, as vaccination is the only sustainable defense. Vaccines need to be safe, efficient, and cost-effective, which is influenced by our understanding of the host–pathogen interface. Additionally, some of the major challenges of vaccines are the establishment of a long-lasting immunity offering cross protection to emerging strains. Although many NSVs are controlled through immunisations, for some, vaccine design has failed or efficacy has proven unreliable. The key behind designing a successful vaccine is understanding the host–pathogen interaction and the host immune response towards NSVs. In this paper, we review the recent research in vaccine design against NSVs and explore the immune responses induced by these viruses. The generation of a robust and integrated approach to development capability and vaccine manufacture can collaboratively support the management of outbreaking NSV disease health risks.
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Chapagain, Pratima, Ali Ali, and Mohamed Salem. "Dual RNA-Seq of Flavobacterium psychrophilum and Its Outer Membrane Vesicles Distinguishes Genes Associated with Susceptibility to Bacterial Cold-Water Disease in Rainbow Trout (Oncorhynchus mykiss)." Pathogens 12, no. 3 (March 10, 2023): 436. http://dx.doi.org/10.3390/pathogens12030436.
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Flavobacterium psychrophilum (Fp), the causative agent of Bacterial Cold-Water disease in salmonids, causes substantial losses in aquaculture. Bacterial outer membrane vesicles (OMVs) contain several virulence factors, enzymes, toxins, and nucleic acids and are expected to play an essential role in host–pathogen interactions. In this study, we used transcriptome sequencing, RNA-seq, to investigate the expression abundance of the protein-coding genes in the Fp OMVs versus the Fp whole cell. RNA-seq identified 2190 transcripts expressed in the whole cell and 2046 transcripts in OMVs. Of them, 168 transcripts were uniquely identified in OMVs, 312 transcripts were expressed only in the whole cell, and 1878 transcripts were shared in the two sets. Functional annotation analysis of the OMV-abundant transcripts showed an association with the bacterial translation machinery and histone-like DNA-binding proteins. RNA-Seq of the pathogen transcriptome on day 5 post-infection of Fp-resistant versus Fp-susceptible rainbow trout genetic lines revealed differential gene expression of OMV-enriched genes, suggesting a role for the OMVs in shaping the host–microbe interaction. Interestingly, a cell wall-associated hydrolase (CWH) gene was the most highly expressed gene in OMVs and among the top upregulated transcripts in susceptible fish. The CWH sequence was conserved in 51 different strains of Fp. The study provides insights into the potential role of OMVs in host–pathogen interactions and explores microbial genes essential for virulence and pathogenesis.
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Leclerc, Melen, Julie A. J. Clément, Didier Andrivon, and Frédéric M. Hamelin. "Assessing the effects of quantitative host resistance on the life-history traits of sporulating parasites with growing lesions." Proceedings of the Royal Society B: Biological Sciences 286, no. 1912 (October 2, 2019): 20191244. http://dx.doi.org/10.1098/rspb.2019.1244.
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Assessing life-history traits of parasites on resistant hosts is crucial in evolutionary ecology. In the particular case of sporulating pathogens with growing lesions, phenotyping is difficult because one needs to disentangle properly pathogen spread from sporulation. By considering Phytophthora infestans on potato, we use mathematical modelling to tackle this issue and refine the assessment of pathogen response to quantitative host resistance. We elaborate a parsimonious leaf-scale model by convolving a lesion growth model and a sporulation function, after a latency period. This model is fitted to data obtained on two isolates inoculated on three cultivars with contrasted resistance level. Our results confirm a significant host–pathogen interaction on the various estimated traits, and a reduction of both pathogen spread and spore production, induced by host resistance. Most interestingly, we highlight that quantitative resistance also changes the sporulation function, the mode of which is significantly time-lagged. This alteration of the infectious period distribution on resistant hosts may have strong impacts on the dynamics of parasite populations, and should be considered when assessing the durability of disease control tactics based on plant resistance management. This inter-disciplinary work also supports the relevance of mechanistic models for analysing phenotypic data of plant–pathogen interactions.
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Singh, Vinayak, Rupal Rai, Bijina J. Mathew, Rashmi Chourasia, Anirudh K. Singh, Awanish Kumar, and Shivendra K. Chaurasiya. "Phospholipase C: underrated players in microbial infections." Frontiers in Cellular and Infection Microbiology 13 (April 17, 2023). http://dx.doi.org/10.3389/fcimb.2023.1089374.
Full textAbstract:
During bacterial infections, one or more virulence factors are required to support the survival, growth, and colonization of the pathogen within the host, leading to the symptomatic characteristic of the disease. The outcome of bacterial infections is determined by several factors from both host as well as pathogen origin. Proteins and enzymes involved in cellular signaling are important players in determining the outcome of host–pathogen interactions. phospholipase C (PLCs) participate in cellular signaling and regulation by virtue of their ability to hydrolyze membrane phospholipids into di-acyl-glycerol (DAG) and inositol triphosphate (IP3), which further causes the activation of other signaling pathways involved in various processes, including immune response. A total of 13 PLC isoforms are known so far, differing in their structure, regulation, and tissue-specific distribution. Different PLC isoforms have been implicated in various diseases, including cancer and infectious diseases; however, their roles in infectious diseases are not clearly understood. Many studies have suggested the prominent roles of both host and pathogen-derived PLCs during infections. PLCs have also been shown to contribute towards disease pathogenesis and the onset of disease symptoms. In this review, we have discussed the contribution of PLCs as a determinant of the outcome of host-pathogen interaction and pathogenesis during bacterial infections of human importance.
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Yu, Hong, Li Li, Anthony Huffman, John Beverley, Junguk Hur, Eric Merrell, Hsin-hui Huang, et al. "A new framework for host-pathogen interaction research." Frontiers in Immunology 13 (December 15, 2022). http://dx.doi.org/10.3389/fimmu.2022.1066733.
Full textAbstract:
COVID-19 often manifests with different outcomes in different patients, highlighting the complexity of the host-pathogen interactions involved in manifestations of the disease at the molecular and cellular levels. In this paper, we propose a set of postulates and a framework for systematically understanding complex molecular host-pathogen interaction networks. Specifically, we first propose four host-pathogen interaction (HPI) postulates as the basis for understanding molecular and cellular host-pathogen interactions and their relations to disease outcomes. These four postulates cover the evolutionary dispositions involved in HPIs, the dynamic nature of HPI outcomes, roles that HPI components may occupy leading to such outcomes, and HPI checkpoints that are critical for specific disease outcomes. Based on these postulates, an HPI Postulate and Ontology (HPIPO) framework is proposed to apply interoperable ontologies to systematically model and represent various granular details and knowledge within the scope of the HPI postulates, in a way that will support AI-ready data standardization, sharing, integration, and analysis. As a demonstration, the HPI postulates and the HPIPO framework were applied to study COVID-19 with the Coronavirus Infectious Disease Ontology (CIDO), leading to a novel approach to rational design of drug/vaccine cocktails aimed at interrupting processes occurring at critical host-coronavirus interaction checkpoints. Furthermore, the host-coronavirus protein-protein interactions (PPIs) relevant to COVID-19 were predicted and evaluated based on prior knowledge of curated PPIs and domain-domain interactions, and how such studies can be further explored with the HPI postulates and the HPIPO framework is discussed.
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Lee, Hyun Jae, Athina Georgiadou, Thomas D. Otto, Michael Levin, Lachlan J. Coin, David J. Conway, and Aubrey J. Cunnington. "Transcriptomic Studies of Malaria: a Paradigm for Investigation of Systemic Host-Pathogen Interactions." Microbiology and Molecular Biology Reviews 82, no. 2 (April 25, 2018). http://dx.doi.org/10.1128/mmbr.00071-17.
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SUMMARYTranscriptomics, the analysis of genome-wide RNA expression, is a common approach to investigate host and pathogen processes in infectious diseases. Technical and bioinformatic advances have permitted increasingly thorough analyses of the association of RNA expression with fundamental biology, immunity, pathogenesis, diagnosis, and prognosis. Transcriptomic approaches can now be used to realize a previously unattainable goal, the simultaneous study of RNA expression in host and pathogen, in order to better understand their interactions. This exciting prospect is not without challenges, especially as focus moves from interactionsin vitrounder tightly controlled conditions to tissue- and systems-level interactions in animal models and natural and experimental infections in humans. Here we review the contribution of transcriptomic studies to the understanding of malaria, a parasitic disease which has exerted a major influence on human evolution and continues to cause a huge global burden of disease. We consider malaria a paradigm for the transcriptomic assessment of systemic host-pathogen interactions in humans, because much of the direct host-pathogen interaction occurs within the blood, a readily sampled compartment of the body. We illustrate lessons learned from transcriptomic studies of malaria and how these lessons may guide studies of host-pathogen interactions in other infectious diseases. We propose that the potential of transcriptomic studies to improve the understanding of malaria as a disease remains partly untapped because of limitations in study design rather than as a consequence of technological constraints. Further advances will require the integration of transcriptomic data with analytical approaches from other scientific disciplines, including epidemiology and mathematical modeling.
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Boulanger, Nathalie, and Stephen Wikel. "Induced Transient Immune Tolerance in Ticks and Vertebrate Host: A Keystone of Tick-Borne Diseases?" Frontiers in Immunology 12 (February 12, 2021). http://dx.doi.org/10.3389/fimmu.2021.625993.
Full textAbstract:
Ticks and tick transmitted infectious agents are increasing global public health threats due to increasing abundance, expanding geographic ranges of vectors and pathogens, and emerging tick-borne infectious agents. Greater understanding of tick, host, and pathogen interactions will contribute to development of novel tick control and disease prevention strategies. Tick-borne pathogens adapt in multiple ways to very different tick and vertebrate host environments and defenses. Ticks effectively pharmacomodulate by its saliva host innate and adaptive immune defenses. In this review, we examine the idea that successful synergy between tick and tick-borne pathogen results in host immune tolerance that facilitates successful tick infection and feeding, creates a favorable site for pathogen introduction, modulates cutaneous and systemic immune defenses to establish infection, and contributes to successful long-term infection. Tick, host, and pathogen elements examined here include interaction of tick innate immunity and microbiome with tick-borne pathogens; tick modulation of host cutaneous defenses prior to pathogen transmission; how tick and pathogen target vertebrate host defenses that lead to different modes of interaction and host infection status (reservoir, incompetent, resistant, clinically ill); tick saliva bioactive molecules as important factors in determining those pathogens for which the tick is a competent vector; and, the need for translational studies to advance this field of study. Gaps in our understanding of these relationships are identified, that if successfully addressed, can advance the development of strategies to successfully disrupt both tick feeding and pathogen transmission.