Influenza is a serious world-wide concern that annually affects 20% of children and 5% of adults. Current vaccinations are effective for healthy adults, but offer a low rate of protection (<40%) for high risk groups including the very old, very young and immunocompromised. A better understanding of the factors affecting the establishment and quality of immunological memory to the virus is needed to design better therapies and preventative measures. We have developed a social stress model, Social Disruption (SDR), that induces glucocorticoid resistance in splenocytes and results in a significantly more reactive pro-inflammatory cytokine environment. Preliminary experiments show that when this stressor is applied prior to a primary influenza infection, there is faster cessation of viral replication and increased expression of type I interferons. During the memory phase, SDR mice have a greater delayed-type hypersensitivity response to a footpad antigen challenge. Upon reinfection/challenge, there is a more numerous virus-specific T cell response. The goal of this grant proposal is to determine the mechanisms by which this social stressor enhances the development of virus specific memory T cell responses. The inter-disciplinary research plan detailed in this application will lead to a more complex grasp of factors able to positively regulate the immune response to a viral challenge. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30DE017068-03
Application #
7587420
Study Section
NIDCR Special Grants Review Committee (DSR)
Program Officer
Frieden, Leslie A
Project Start
2006-09-01
Project End
2009-08-31
Budget Start
2008-09-01
Budget End
2009-08-31
Support Year
3
Fiscal Year
2008
Total Cost
$25,772
Indirect Cost
Name
Ohio State University
Department
Dentistry
Type
Schools of Dentistry
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
Mays, Jacqueline W; Powell, Nicole D; Hunzeker, John T et al. (2012) Stress and the anti-influenza immune response: repeated social defeat augments clonal expansion of CD8(+)T cells during primary influenza A viral infection. J Neuroimmunol 243:34-42
Avitsur, Ronit; Mays, Jacqueline W; Sheridan, John F (2011) Sex differences in the response to influenza virus infection: modulation by stress. Horm Behav 59:257-64
Mays, Jacqueline W; Bailey, Michael T; Hunzeker, John T et al. (2010) Influenza virus-specific immunological memory is enhanced by repeated social defeat. J Immunol 184:2014-25