Influenza virus poses a major threat to human health. It also predisposes to superinfection of the respiratory tract (RT), most commonly by Streptococcus pneumonia, and is responsible for . significant morbidity and mortality, particularly in the young and elderly. B cells play a vital role in immunity to influenza virus, highlighted by the production of viral-neutralizing antibodies and in the efficacy of influenza vaccines. While it is appreciated that B cells play a critical role in the host response to influenza virus, less is known about the nature of the protective humoral response in the RT. Our project proposes to comprehensively analyze and compare the B cell response in the lung to influenza virus under conditions of viral infection with or without bacterial co-infection as well as vaccination. We hypothesize that the B cell response to influenza virus will have distinct signatures in these divergent contexts. Emphasis will be placed on features of the local RT immunity that promote anti-influenza B cell survival, maturation and differentiation. We will also identify the mechanisms that govern the development, recruitment and maintenance of plasma cells (PC) in the RT. While short-term PC may participate in rapid first line of host defense, long-term PCs and memory cells are critical for the development of lasting protection. By defining the anti-influenza response in situ where the virus infects lung epithelial cells, we may be better equipped to induce targeted mucosal protection through vaccination.
Influenza virus remains a major threat to human health. While it is appreciated that B cells play a critical role in the host response to this virus, little is known about the nature of the protective B cell response in the respiratory tract. This project proposes to investigate how the B cell response to influenza virus is induced and regulated with the goal of identifying critical interactions responsible for effective immunity.
|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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