Tuberculosis remains the world's leading infectious cause of death, and the rise of multidrug resistant tuberculosis and the interaction of the TB and AIDS epidemics worldwide are creating a public health threat of massive proportions. In recent years, we have pursued studies aimed at elucidating ways in which the host immune response to tuberculosis may offer protection from the disease, as well as ways in which inflammatory responses can be modified to improve outcomes in patients with multidrug resistant tuberculosis. We have demonstrated that the cytokine interferon (IFN) gamma plays a major role in human host defense against tuberculosis; a detailed understanding of immune mechanisms upstream and downstream from IFN's action in patients should provide significant insight into protection against tuberculosis infection and disease. To that end, three specific aims are planned:
Specific aim 1 : To assess, by determining the types and levels of chemokine present in bronchoalveolar lavage fluid of patients with tuberculosis, the signals in the lung which may cause recruitment of immune effector cells associated with an effective host response.
Specific aim 2 : To assess the state of activation of antigen presenting cell as well as immune effector cells in the lungs of patients with tuberculosis compared to controls.
Specific aim 3 : To assess changes in the pulmonary host response after administration of interferon gamma by aerosol to clearly define the mechanisms by which IFN causes clinical improvement in tuberculosis patients.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24HL004074-05
Application #
6656932
Study Section
Special Emphasis Panel (ZHL1-CSR-F (M3))
Program Officer
Colombini-Hatch, Sandra
Project Start
1999-09-20
Project End
2004-07-31
Budget Start
2003-08-01
Budget End
2004-07-31
Support Year
5
Fiscal Year
2003
Total Cost
$112,730
Indirect Cost
Name
Columbia University (N.Y.)
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Schluger, Neil W; Burzynski, Joseph (2010) Recent advances in testing for latent TB. Chest 138:1456-63
Lopez de Castilla, D; Schluger, N W (2010) Tuberculosis following solid organ transplantation. Transpl Infect Dis 12:106-12
Ben Amor, Yanis; Nemser, Bennett; Singh, Angad et al. (2008) Underreported threat of multidrug-resistant tuberculosis in Africa. Emerg Infect Dis 14:1345-52
Brodie, Daniel; Lederer, David J; Gallardo, Jade S et al. (2008) Use of an interferon-gamma release assay to diagnose latent tuberculosis infection in foreign-born patients. Chest 133:869-74
Schluger, Neil W (2007) Tuberculosis and nontuberculous mycobacterial infections in older adults. Clin Chest Med 28:773-81, vi
Schluger, Neil W (2005) The pathogenesis of tuberculosis: the first one hundred (and twenty-three) years. Am J Respir Cell Mol Biol 32:251-6
Geng, Elvin; Kreiswirth, Barry; Burzynski, Joe et al. (2005) Clinical and radiographic correlates of primary and reactivation tuberculosis: a molecular epidemiology study. JAMA 293:2740-5
Schluger, Neil W; Perez, Daniel; Liu, Yuk Ming (2002) Reconstitution of immune responses to tuberculosis in patients with HIV infection who receive antiretroviral therapy. Chest 122:597-602
Geng, Elvin; Kreiswirth, Barry; Driver, Cynthia et al. (2002) Changes in the transmission of tuberculosis in New York City from 1990 to 1999. N Engl J Med 346:1453-8
Schluger, N W (2001) Changing approaches to the diagnosis of tuberculosis. Am J Respir Crit Care Med 164:2020-4