This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Abstract: Mycobacterium tuberculosis (Mtb) infects two billion people worldwide. Alcoholics have a greater burden of TB than normal hosts, and alcohol worsens the progression and the outcome of the disease. Nonhuman primates best recapitulate the human TB syndrome, and Dr. Kaushal's group at the TNPRC has generated a model of human TB in macaques exposed to aerosolized Mtb [Dutta et al, J. Infect Dis, 2010, 201:]. Further, the Comprehensive Alcohol Research Center (CARC) at the LSU School of Medicine, New Orleans has considerable expertise in studying co-incident infectious diseases in a nonhuman primate model of binge alcoholism. We hypothesize that binge alcohol consumption by rhesus macaques will adversely affect the containment of virulent Mtb via alterations in the lung CD4+ Th1 effector cell number and function, causing accelerated progression of infection. We propose the following specific aims: 1. To evaluate the mycobacterial clearance of pulmonary infection with virulent Mtb in alcohol consuming rhesus monkeys. 2. Characterize the immune response in these animals as well as gene expression through transcriptomics. This project has been funded, and is expected to start as soon as appropriate BSL-3 space is available.
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