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.
