Viral infections remain a considerable cause of morbidity and mortality. Despite advances in the availability of vaccines, the mechanisms of generating and maintaining effective antiviral immunity remains incompletely understood. A major concern in this regard is influenza virus, a focal point for a number of Projects in this Program. The vaccine for influenza virus must be remade each year because it has not yet been possible to generate broadly protective immunity to this rapidly evolving RNA virus and the potential emergence of devastating pandemic influenza virus strains remains ever present. Thus, it is essential that we understand the basic principles of long-term B cell and T cell immunity to viral infections, including influenza virus, to improve existing, and develop novel, vaccination strategies. A major complication with influenza virus infection is co-infection with bacteria resulting in bacterial pneumonia. It is unclear how such a co-infection with a virus and bacterial pathogen in the respiratory tract impacts antiviral immunological memory and future protective immunity to the virus. To address these questions, the research Projects will utilize common infectious agents. The overall goal of Core B is to generate, standardize, store and provide infectious agents to the Projects. In addition, Core B will optimize and validate assays to monitor the burden of infectious agents in tissues from infected animals. Thus, the specific Aims for this core are: 1) To define a model of respiratory infection with Streptococcus pneumonia (Sp) and coinfection with Sp and influenza virus;2) To generate and characterize Streptococcus pneumoniae expressing CD4 T cell determinant(s) from influenza virus HA;and 3) To produce, standardize, maintain and store infectious agents. The activities of this Core will therefore create synergy and interaction between the different Projects by creating a common and easily accessible set of tools, and by enhancing the quality, standardization and reproducibility of the data generated by the individual Projects.

Public Health Relevance

Influenza virus remains a major human pathogen and the threat of the emergence of pandemic strains remains ever present. In addition, a major complication during influenza virus infection is co-infection with respiratory bacterial infections. To investigate the mechanisms of immunity to influenza virus and to begin to understand the immunological impact of co-infection, Core B will provide infectious agents to the Projects.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
1U19AI083022-01
Application #
7746174
Study Section
Special Emphasis Panel (ZAI1-BDP-I (J3))
Project Start
2009-05-01
Project End
2014-04-30
Budget Start
2009-03-01
Budget End
2010-04-30
Support Year
1
Fiscal Year
2009
Total Cost
$185,860
Indirect Cost
Name
Wistar Institute
Department
Type
DUNS #
075524595
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Wang, Y; Jiang, B; Guo, Y et al. (2017) Cross-protective mucosal immunity mediated by memory Th17 cells against Streptococcus pneumoniae lung infection. Mucosal Immunol 10:250-259
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
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 135:2688-2696
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
Chang, John T; Wherry, E John; Goldrath, Ananda W (2014) Molecular regulation of effector and memory T cell differentiation. Nat Immunol 15:1104-15
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
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

Showing the most recent 10 out of 53 publications