Influenzae A virus (IAV) is highly contagious and is responsible for outbreaks of seasonal flu. In humans, IAV infection is usually confined to the epithelia of nasopharynx, trachea and large bronchi. Only in some cases does the infection progress to a primary viral pneumonia. However, secondary bacterial pneumonia is a frequent and serious complication with high mortality. In addition to annual influenza epidemics, there is an ever-present threat of a global pandemic and several recent pandemics have inflicted widespread devastation. In the majority of cases, the high mortality associated with these influenza pandemics is not due to primary viral pneumonia, but is instead caused by secondary bacterial infections. Streptococcus pneumoniae (Sp) is a Gram-positive bacterium that is the leading cause of secondary bacterial pneumonia associated with both influenza epidemics and pandemics. The effect of IAV infection on host susceptibility to Sp has been studied extensively in the murine model. However, limited information is available on how Sp may affect the course of IAV infection, and consequently, disease outcome. Even less is known about how Sp co-infection may affect the generation of immunological memory and anti-flu immunity. Our recent results have shown that inflammation induced by a bacterial pathogen can have opposing effects on different phases of the adaptive immune response. These results have important implications that are particularly relevant to co-infection where inflammatory responses induced by one pathogen can have bystander effects on the other pathogen. As such, we hypothesize that inflammation induced by Sp could alter host resistance/susceptibility to IAV and influence the lAV-specific adaptive immune response. We will test our hypothesis by 1) determining the effect of Sp co-infection on host resistance/susceptibility to IAV infection, 2) studying the role of inflammatory responses in mediating protection or immunopathology during lAV/Sp coinfection, 3) determine the effect of Sp co-infection on CDS T cell responses to IAV and lAV-specific CDS T cell memory. At the end of this study, we hope to gain a better understanding of the complex host-virusbacterium interactions occuring during co-infection, with the goal of developing interventions that will shift the balance of the interaction to benefit the host.
Second bacterial pneumonia is a serious complication during and shortly after influenza A infection. Understadning how a bacterial co-infection may affect host resistance to influenza virus will help us develop novel strategies to treat the severe diseases and prevent mortality caused by secondary bacterial pneumonia associated with flu infection.
|Wang, Y; Jiang, B; Guo, Y et al. (2016) Cross-protective mucosal immunity mediated by memory Th17 cells against Streptococcus pneumoniae lung infection. Mucosal Immunol :|
|Thome, Joseph J C; Bickham, Kara L; Ohmura, Yoshiaki et al. (2016) Early-life compartmentalization of human T cell differentiation and regulatory function in mucosal and lymphoid tissues. Nat Med 22:72-7|
|Yang, Cheng; Khanniche, Asma; DiSpirito, Joanna R et al. (2016) Transcriptome Signatures Reveal Rapid Induction of Immune-Responsive Genes in Human Memory CD8(+) T Cells. Sci Rep 6:27005|
|Crosby, Erika J; Clark, Megan; Novais, Fernanda O et al. (2015) Lymphocytic Choriomeningitis Virus Expands a Population of NKG2D+CD8+ T Cells That Exacerbates Disease in Mice Coinfected with Leishmania major. J Immunol 195:3301-10|
|Zens, Kyra D; Farber, Donna L (2015) Memory CD4 T cells in influenza. Curr Top Microbiol Immunol 386:399-421|
|Weissler, Katherine A; Garcia, Victoria; Kropf, Elizabeth et al. (2015) Distinct modes of antigen presentation promote the formation, differentiation, and activity of foxp3+ regulatory T cells in vivo. J Immunol 194:3784-97|
|Yu, Minjun; Owens, David M; Ghosh, Sankar et al. (2015) Conditional PDK1 Ablation Promotes Epidermal and T-Cell-Mediated Dysfunctions Leading to Inflammatory Skin Disease. J Invest Dermatol 135:2688-96|
|Lee, JangEun; Walsh, Matthew C; Hoehn, Kyle L et al. (2014) Regulator of fatty acid metabolism, acetyl coenzyme a carboxylase 1, controls T cell immunity. J Immunol 192:3190-9|
|Beiting, Daniel P; Peixoto, Lucia; Akopyants, Natalia S et al. (2014) Differential induction of TLR3-dependent innate immune signaling by closely related parasite species. PLoS One 9:e88398|
|Wolf, Amaya I; Strauman, Maura C; Mozdzanowska, Krystyna et al. (2014) Pneumolysin expression by streptococcus pneumoniae protects colonized mice from influenza virus-induced disease. Virology 462-463:254-65|
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