Abstract

The hypothesis of this proposal is that the interaction of tuberculosis and HIV during active tuberculosis and at sites of M.tuberculosis infection, predisposes the host to progression of HIV disease through both virologic and immunologic events and that the interaction of macrophages with T cells plays a central,role in this process.
The specific aims of the proposal are 1. Determination of the role of the interaction of macrophages with T-cells in supporting expansion of HIV burden and enhanced HIV cytopathicity in patients with tuberculosis. 2. Determination of HIV genotype (V3 loop heterogeneity) and phenotype (SI/NSI and co-receptor usage) both systematically and locally in HIV-infected patients with tuberculosis. 3. Determination of anti-HIV cellular (CD4 and CD8) and humoral (neutralizing antibody) immune reponses at the time of diagnosis of tuberculosis both systemically and locally in HIV infected patients with tuberculosis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL051636-07
Application #
6183424
Study Section
Special Emphasis Panel (ZRG5-AARR-4 (01))
Project Start
1993-09-30
Project End
2004-07-31
Budget Start
2000-08-01
Budget End
2001-07-31
Support Year
7
Fiscal Year
2000
Total Cost
$278,675
Indirect Cost

  Institution

Name
Case Western Reserve University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106

  Publications

Hirsch, Christina S; Rojas, Roxana; Wu, Mianda et al. (2016) Mycobacterium tuberculosis Induces Expansion of Foxp3 Positive CD4 T-cells with a Regulatory Profile in Tuberculin Non-sensitized Healthy Subjects: Implications for Effective Immunization against TB. J Clin Cell Immunol 7:
Meng, Qinglai; Canaday, David H; McDonald, David J et al. (2016) Productive HIV-1 infection is enriched in CD4(-)CD8(-) double negative (DN) T cells at pleural sites of dual infection with HIV and Mycobacterium tuberculosis. Arch Virol 161:181-7
Hirsch, Christina S; Baseke, Joy; Kafuluma, John Lusiba et al. (2016) Expansion and productive HIV-1 infection of Foxp3 positive CD4 T cells at pleural sites of HIV/TB co-infection. J Clin Exp Immunol 1:
Toossi, Zahra; Meng, Qinglai; Aung, Htin et al. (2015) Short Communication: Expression of APOBEC3G and Interferon Gamma in Pleural Fluid Mononuclear Cells from HIV/TB Dual Infected Subjects. AIDS Res Hum Retroviruses 31:692-5
Toossi, Zahra; Wu, Mianda; Liu, Shigou et al. (2014) Role of protease inhibitor 9 in survival and replication of Mycobacterium tuberculosis in mononuclear phagocytes from HIV-1-infected patients. AIDS 28:679-87
Toossi, Zahra; Wu, Mianda; Hirsch, Christina S et al. (2012) Activation of P-TEFb at sites of dual HIV/TB infection, and inhibition of MTB-induced HIV transcriptional activation by the inhibitor of CDK9, Indirubin-3'-monoxime. AIDS Res Hum Retroviruses 28:182-7
Toossi, Zahra; Wu, Mianda; Rojas, Roxana et al. (2012) Induction of serine protease inhibitor 9 by Mycobacterium tuberculosis inhibits apoptosis and promotes survival of infected macrophages. J Infect Dis 205:144-51
Wu, M; Aung, H; Hirsch, C S et al. (2012) Inhibition of Mycobacterium tuberculosis-induced signalling by transforming growth factor-? in human mononuclear phagocytes. Scand J Immunol 75:301-4
Toossi, Z; Hirsch, C S; Wu, M et al. (2011) Distinct cytokine and regulatory T cell profile at pleural sites of dual HIV/tuberculosis infection compared to that in the systemic circulation. Clin Exp Immunol 163:333-8
El Fenniri, L; Toossi, Z; Aung, H et al. (2011) Polyfunctional Mycobacterium tuberculosis-specific effector memory CD4+ T cells at sites of pleural TB. Tuberculosis (Edinb) 91:224-30

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