Chronic Tuberculosis: Latent or Dynamic

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DESCRIPTION (provided by applicant): This proposal from the Mycobacteria Research Laboratories, Colorado State University, is for competitive renewal of program AI-44072, "Chronic tuberculosis: latent or dynamic?" which in the previous funding period has made substantial progress in each of its Aims. In this new proposal, we wish to continue to try to define the immunological mechanisms that control and maintain the integrity of the chronic disease state, which we believe will ultimately provide a better understanding of the basis of latent tuberculosis in humans. In this proposal the first objective is to better define the role of IL-10, and to determine its potential role in reactivation disease in mouse strains prone to this event. The second Aim is to continue our studies on the role of CD8 T cells during the chronic disease state, given the accumulating evidence that they play an important role in maintaining the integrity of this process. A third Aim takes advantage of a new microarray laboratory recently established in the MRL. Using this facility we intend to try to provide a global picture of gene expression [concentrating initially on cytokines, chemokines, and their receptors] as the immune response in the lungs develops from containment, through the chronic disease state. Finally, in a fourth Aim, we propose to continue to develop new animal models that may provide new information about chronic/latent tuberculosis. The proposed work will take advantage of the advanced biosafety level III facilities at CSU, the broad expertise of various members of the Mycobacteria Research Laboratories, CSU, as well as a number of highly qualified consultants collaborators.