INTERACTION OF M TUBERCULOSIS AND HIV IN THE LUNG

这项提案的目标是审查积极的 结核病对人类免疫缺陷病毒(HIV)表达的影响 感染，并审查艾滋病毒-M的后果。结核病 对肺损伤的相互作用。结核病是艾滋病毒的一种主要感染方式 全世界的血清阳性人群，这对艾滋病毒疾病产生了不利影响 与艾滋病相比，更早发生在艾滋病毒疾病的病程中- 相关的机会性感染。我们在未感染艾滋病毒的人群中的研究 活动性肺结核患者表明血液 单核细胞容易感染艾滋病毒，这可能 与它们在体内(启动)细胞因子表达有关。分枝杆菌 产品诱导单核细胞因子，并增强HIV在 潜伏感染HIV的单核细胞系和原代单核细胞 在体外感染艾滋病毒。 这一提议的假设是单核细胞的激活 在结核病期间和由结核分枝杆菌及其产品增强 潜伏感染或新感染的细胞产生艾滋病毒，以及 HIV病毒由此产生的增强干扰了适当的肉芽肿 对结核分枝杆菌的反应。该提案的具体目的是寻求 目的：阐明结核患者单核细胞的基础，以及 结核分枝杆菌有利于艾滋病毒的复制，以及病毒和 细胞因子活性影响肺泡细胞损伤和肺泡炎的形成 肉芽肿。这项建议的具体目标是： 具体目标1：检查增强的分子基础 HIV血清阴性活动期患者单核细胞易感性的研究 结核病对艾滋病毒的生产性感染。 特定目标2：确定结核分枝杆菌对基因表达的影响 正常人外周血单核细胞和肺泡巨噬细胞对病毒活性的影响 在体外感染艾滋病毒后的个人，以及来自艾滋病毒的- 被感染的人。 具体目标3：检查增强的病毒表达和 HIV和M.相互作用导致细胞因子活性增强。 肺结核对肺泡上皮细胞和非细胞的损伤 多核巨细胞(MGC)的形成。

The objectives of this proposal are to examine the impact of active tuberculosis on expression of Human Immunodeficiency Virus (HIV) infection, and to examine the consequences of HIV-M. tuberculosis interaction on lung injury. Tuberculosis is a major infection in HIV seropositive populations worldwide, which adversely affects HIV disease and occurs earlier in the course of HIV disease as compared to AIDS- related opportunistic infections. Our studies in the HIV-uninfected population with active pulmonary tuberculosis indicate that blood monocytes are susceptible to a productive infection with HIV, which may relate to their in vivo (priming) for cytokine expression. Mycobacterial products induce monocyte cytokines, and augment HIV expression in monocytoid cell lines latently infected with HIV, and primary monocytes infected with HIV in vitro. The hypothesis of this proposal is that activation of mononuclear cells during tuberculosis and by M. tuberculosis and its products enhances production of HIV by latently-infected or newly-infected cells, and the resulting augmentation in HIV interferes with a proper granulomatous response against M. tuberculosis. The specific aims of the proposal seek to elucidate the basis by which monocytes from tuberculous patients, and M. tuberculosis favor replication of HIV and how amplified viral and cytokine activity affects alveolar cell damage and formation of granulomas. The Specific Aims of this proposal are: Specific Aim 1: To examine the molecular basis for the enhanced susceptibility of monocytes from HIV-seronegative patients with active tuberculosis to a productive infection with HIV. Specific Aim 2: To determine the effect of M. tuberculosis on expression of viral activity by blood monocytes and alveolar macrophages from healthy individuals subsequent to in vitro infection with HIV, and from HIV- infected individuals. Specific Aim 3: To examine the effects of enhanced viral expression and amplified cytokine activity resulting from the interaction of HIV and M. tuberculosis on damage to alveolar epithelial cells and noncellular matrix, and on formation of multinucleated giant cells (MGC).