Abstract

The incidence of tuberculosis in the United States has increased during the past 10 years and tuberculOsis continues to be a significant public health problem world wide. Most individuals who are infected with Mycobacterium tuberculosis develop a cell mediated immune response and control the disease. Infected individuals stand a 10% lifetime chance of the disease reactivating. Conventional wisdom has attributed reactivation to a temporary suppression Of the immune response which allows the microorganisms to grow. Among the factors thought to be responsible for reactivation of Mycobacterial growth are infection with the human immunodeficiency virus, immunosenesence due to aging, protein malnutrition associated with chronic alcoholism and stress. The purpose of this investigation is to evaluate the effects of stress on the reactivation of Mycobacterium tuberculosis growth in a mouse model. We will test the hypothesis that stress serves as a cofactor in reactivation by altering T cell and macrophage mediated control of Mycobacterial growth.
Our specific aims are: l. To determine the effect of restraint stress on reactivation of the growth of Mycobacterium tuberculosis; 2. To determine the changes in T cell mediated immunity as a result of restraint stress that results in the growth of Mycobacterium tuberculosis, and 3. To determine the changes in macrophage mediated control of Mycobacterium tuberculosis growth that results from restraint stress.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH054966-05
Application #
2890732
Study Section
Special Emphasis Panel (SRCM (15))
Program Officer
Muehrer, Peter R
Project Start
1995-09-01
Project End
2000-04-30
Budget Start
1999-05-01
Budget End
2000-04-30
Support Year
5
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Ohio State University
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210

  Publications

Lafuse, W P; Alvarez, G R; Zwilling, B S (2000) Regulation of Nramp1 mRNA stability by oxidants and protein kinase C in RAW264.7 macrophages expressing Nramp1(Gly169). Biochem J 351 Pt 3:687-96
Wang, T; Lafuse, W P; Zwilling, B S (2000) Regulation of toll-like receptor 2 expression by macrophages following Mycobacterium avium infection. J Immunol 165:6308-13
Hussain, S; Zwilling, B S; Lafuse, W P (1999) Mycobacterium avium infection of mouse macrophages inhibits IFN-gamma Janus kinase-STAT signaling and gene induction by down-regulation of the IFN-gamma receptor. J Immunol 163:2041-8
Zwilling, B S; Kuhn, D E; Wikoff, L et al. (1999) Role of iron in Nramp1-mediated inhibition of mycobacterial growth. Infect Immun 67:1386-92
Chen, L; Boomershine, C; Wang, T et al. (1999) Synergistic interaction of catecholamine hormones and Mycobacterium avium results in the induction of interleukin-10 mRNA expression by murine peritoneal macrophages. J Neuroimmunol 93:149-55
Boomershine, C S; Lafuse, W P; Zwilling, B S (1999) Beta2-adrenergic receptor stimulation inhibits nitric oxide generation by Mycobacterium avium infected macrophages. J Neuroimmunol 101:68-75
Kuhn, D E; Baker, B D; Lafuse, W P et al. (1999) Differential iron transport into phagosomes isolated from the RAW264.7 macrophage cell lines transfected with Nramp1Gly169 or Nramp1Asp169. J Leukoc Biol 66:113-9
Howard, A D; Zwilling, B S (1999) Reactivation of tuberculosis is associated with a shift from type 1 to type 2 cytokines. Clin Exp Immunol 115:428-34
Howard, A D; Zwilling, B S (1998) Cytokine production by CD4 and CD8 T cells during the growth of Mycobacterium tuberculosis in mice. Clin Exp Immunol 113:443-9
Brown, D H; Lafuse, W P; Zwilling, B S (1998) Host resistance to mycobacteria is compromised by activation of the hypothalamic-pituitary-adrenal axis. Ann N Y Acad Sci 840:773-86

Showing the most recent 10 out of 12 publications