Although generally thought of as distinct, the nervous, endocrine, and immune systems are intimately related. In particular, the activation of the hypothalamic-pituitary-adrenal (HPA) axis by psychological stress has been shown to inhibit the immune response to herpes simplex virus type-1 (HSV-1) in the periphery. However, previous studies have shown that stress increases the immune response to HSV-1 in the brain, resulting in increased CD8+T cell infiltration and the subsequent development of HSV-1 encephalitis (HSE). The mechanisms underlying the infiltration of CD8+ T cells into the brain during HSE, however, have not yet been elucidated. The proposed research seeks to determine the role of microglia, the primary immune mediators of the central nervous system (CNS), in the attraction and activation of CD8+T cells during HSE by examining the following specific aims: (1) To determine microglia TH1/TH2 cytokine and chemokine production during stress-induced HSE and (2) To determine microglia MHC class I presentation and expression of co-stimulatory molecules during stress-induced HSE. These studies will test the hypothesis that enhanced microglia activation during stress increases the infiltration and activation of CD8+T cells during HSV-1 infection, thus promoting the development of HSE. Microglia may contribute to CD8+ T cell infiltration by generating a pro-inflammatory environment through TH1 cytokine and chemokine production, as well as by activating T cells with MHC class I/peptide complexes and costimulatory molecules. Overall, the proposed studies will determine the role of stress in enhancing neuroinflammation during HSV-1 infection through its actions on microglia activation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31MH072096-02
Application #
6934600
Study Section
Special Emphasis Panel (ZRG1-F02A (20))
Program Officer
Stoff, David M
Project Start
2004-08-01
Project End
2006-07-31
Budget Start
2005-08-01
Budget End
2006-07-31
Support Year
2
Fiscal Year
2005
Total Cost
$27,050
Indirect Cost
Name
Pennsylvania State University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033