Infection with the human immunodeficiency virus leads to a systemic immunosuppression that results in an increase in the susceptibility of the host to infection. Infection by opportunistic pathogens is responsible for the morbidity and mortality associated with AIDS. The incidence of mycobacterial diseases, including infections caused by M tuberculosis and avium, has increased significantly among HIV-infected individuals. Studies in the investigator's laboratory have correlated differences in MHC class II expression with resistance to mycobacterial growth in mice. Similar differences in MHC class II expression by human monocytes have been identified also by the investigators. Stress may be an important cofactor in susceptibility to mycobacterial disease, and this laboratory has shown that restraint stress results in a suppression of Ia expression. Differences in Ia expression indicate that there may be differences in the level of activation of the macrophages in mice that are resistant or susceptible to mycobacterial growth. The purpose of this renewal application will be to determine the role of stress in modulating the pathogenesis of mycobacterial infection and to correlate these differences to changes in Ia expression. Thus, restraint stress may alter the host parasite relationship by allowing the opportunistic pathogen to become established and grown within mononuclear phagocytes.
The specific aims are: (1) to determine the effect of restraint on the growth of Mycobacteria in vivo; (2) to determine whether restraint stress induced alteration in mycobacterial growth is mediated by the hypothalamic-pituitary-adrenal axis; (3) to determine the role of the sympathetic nervous system in restraint stress mediated alteration in mycobacterial growth; (4) to determine the effect of restraint stress on the in vitro activity of macrophages; and (5) to determine the mechanism of restraint stress mediated alteration in macrophage function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
2R01MH045679-04
Application #
3385490
Study Section
Psychobiological, Biological, and Neurosciences Subcommittee (MHAI)
Project Start
1989-08-01
Project End
1997-08-31
Budget Start
1992-09-01
Budget End
1993-08-31
Support Year
4
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Ohio State University
Department
Type
Schools of Arts and Sciences
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210
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Brown, D H; Zwilling, B S (1994) Activation of the hypothalamic-pituitary-adrenal axis differentially affects the anti-mycobacterial activity of macrophages from BCG-resistant and susceptible mice. J Neuroimmunol 53:181-7
Brown, D; Faris, M; Hilburger, M et al. (1994) The induction of persistence of I-A expression by macrophages from Bcgr mice occurs via a protein kinase C-dependent pathway. J Immunol 152:1323-31
Zwilling, B S; Brown, D; Feng, N et al. (1993) The effect of adrenalectomy on the restraint stressed induced suppression of MHC class II expression by murine peritoneal macrophages. Brain Behav Immun 7:29-35
Brown, D H; Sheridan, J; Pearl, D et al. (1993) Regulation of mycobacterial growth by the hypothalamus-pituitary-adrenal axis: differential responses of Mycobacterium bovis BCG-resistant and -susceptible mice. Infect Immun 61:4793-800
McPeek, M; Salkowitz, J; Laufman, H et al. (1992) The expression of HLA-DR by monocytes from black and from white donors: different requirements for protein synthesis. Clin Exp Immunol 87:163-8
Zwilling, B S; Lafuse, W P; Brown, D et al. (1992) Characterization of ACTH mediated suppression of MHC class II expression by murine peritoneal macrophages. J Neuroimmunol 39:133-8
Faris, M; Zwilling, B S (1991) Characterization of the induction of persistence of major histocompatibility complex class II by hybrids of macrophages from bacillus Calmette Guerin-resistant mice. Eur J Immunol 21:1047-52
Faris, M; Zwilling, B S (1991) Characterization of the induction of persistent I-A expression by macrophages from Bcgr mice. J Leukoc Biol 49:289-93

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