The recent tuberculosis (TB) epidemic in the United States has been fueled by several factors, including underfunded public health programs, overcrowding in urban homeless shelters and prisons, continuing immigration to the United States from countries with a high incidence of TB, and the HIV epidemic. The increased susceptibility to tuberculosis infection and disease among HIV-infected patients is directly related to impaired host immunity. In recent years, key components of the host response to tuberculosis have been elucidated, and it now seems increasingly clear that a Th1-type T-lymphocyte response is associated with a good outcome in TB patients. In addition, there is increasing evidence that HIV-infected patients have impaired TH1 number and function, with a resultant deficiency of interferon-gamma (IFN-g), a key effector cytokine in host immunity in tuberculosis. This project proposes to study the role of T-helper cells in human tuberculosis, with a specific focus on the role of IFN-g in the pathogenesis of tuberculosis in patients with and without HIV infection. This project will study the role of Th1 cells in general and IFN-g in particular both at the clinical level as well as at the basic level so that we might understand both the regulation of gene expression of this cytokine as well as its interaction with other cytokines and inflammatory effector cells in the lung itself, both in HIV positive and negative patients.
The specific aims are to: 1) modulate the Th phenotype in BAL cells and HIV-1 replication in active pulmonary tuberculosis by aerosol treatment with interferon-gamma; 2) investigate mechanisms by which IFN-gamma contributes to host defense against tuberculosis in HIV-positive and HIV-negative persons; and 3) analyze mechanisms of gene regulation effected by IFN-gamma treatment.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL059832-01
Application #
2541552
Study Section
Special Emphasis Panel (ZHL1-CSR-H (S1))
Project Start
1997-09-30
Project End
2002-08-31
Budget Start
1997-09-30
Budget End
1998-08-31
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
New York University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10016
Weiden, Michael D; Hoshino, Satomi; Levy, David N et al. (2014) Adenosine deaminase acting on RNA-1 (ADAR1) inhibits HIV-1 replication in human alveolar macrophages. PLoS One 9:e108476
Dawson, Rod; Condos, Rany; Tse, Doris et al. (2009) Immunomodulation with recombinant interferon-gamma1b in pulmonary tuberculosis. PLoS One 4:e6984
Raju, Bindu; Hoshino, Yoshihiko; Belitskaya-Levy, Ilana et al. (2008) Gene expression profiles of bronchoalveolar cells in pulmonary TB. Tuberculosis (Edinb) 88:39-51
Hoshino, Yoshihiko; Hoshino, Satomi; Gold, Jeffrey A et al. (2007) Mechanisms of polymorphonuclear neutrophil-mediated induction of HIV-1 replication in macrophages during pulmonary tuberculosis. J Infect Dis 195:1303-10
Katano, Harutaka; Sato, Yuko; Hoshino, Satomi et al. (2007) Integration of HIV-1 caused STAT3-associated B cell lymphoma in an AIDS patient. Microbes Infect 9:1581-9
Achkar, Jacqueline M; Dong, Yuxin; Holzman, Robert S et al. (2006) Mycobacterium tuberculosis malate synthase- and MPT51-based serodiagnostic assay as an adjunct to rapid identification of pulmonary tuberculosis. Clin Vaccine Immunol 13:1291-3
Tanaka, Naohiko; Hoshino, Yoshihiko; Gold, Jeffrey et al. (2005) Interleukin-10 induces inhibitory C/EBPbeta through STAT-3 and represses HIV-1 transcription in macrophages. Am J Respir Cell Mol Biol 33:406-11
Raju, Bindu; Hoshino, Yoshihiko; Kuwabara, Kenichi et al. (2004) Aerosolized gamma interferon (IFN-gamma) induces expression of the genes encoding the IFN-gamma-inducible 10-kilodalton protein but not inducible nitric oxide synthase in the lung during tuberculosis. Infect Immun 72:1275-83
Condos, Rany; Hull, Frank P; Schluger, Neil W et al. (2004) Regional deposition of aerosolized interferon-gamma in pulmonary tuberculosis. Chest 125:2146-55
Gold, Jeffrey A; Hoshino, Yoshihiko; Tanaka, Naohiko et al. (2004) Surfactant protein A modulates the inflammatory response in macrophages during tuberculosis. Infect Immun 72:645-50

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