ALCOHOL AND TB IN NONHUMAN PRIMATES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 摘要：结核分枝杆菌(Mtb)感染着全球20亿人。与正常宿主相比，酗酒者患结核病的负担更大，酒精会恶化疾病的进展和结局。非人灵长类动物最好地概括了人类结核病综合症，TNPRC的Kaushal博士的团队已经在雾化结核分枝杆菌暴露的猕猴中建立了人类结核病的模型[duta等人，J.Infect Dis，2010,201：]。此外，新奥尔良路易斯安那州立大学医学院的综合酒精研究中心(CARC)在研究狂饮酒精中毒的非人类灵长类动物模型中同时发生的传染病方面拥有相当多的专业知识。 我们推测，恒河猴大量饮酒将通过改变肺内CD4+Th1效应细胞的数量和功能，从而加速感染的进展，从而对毒力结核杆菌的遏制产生不利影响。我们提出了以下具体目标： 1.观察Mtb强毒对饮酒恒河猴肺部感染的清除作用。 2.通过转录组学鉴定这些动物的免疫反应和基因表达。 该项目已获得资金，预计一旦有适当的BSL-3空间可用，就将立即开始。

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.