INTERACTION OF M TUBERCULOSIS AND HIV IN THE LUNG

本建议的目的是审查积极的 结核病对人类免疫缺陷病毒（HIV）表达的影响 感染，并检查HIV-M的后果。结核 肺损伤的相互作用。结核病是艾滋病病毒的主要传染病 对艾滋病毒疾病产生不利影响的 与艾滋病相比，在艾滋病病程中发生得更早， 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 活动性肺结核患者的血液 单核细胞易受HIV感染， 涉及它们在体内（引发）细胞因子表达。 分枝杆菌 产品诱导单核细胞细胞因子，并增加HIV表达， 潜伏感染HIV的单核细胞样细胞系和原代单核细胞 在体外感染艾滋病毒。 该建议的假设是，单核细胞的激活 在结核病和M.结核病及其产物增强了 潜伏感染或新感染的细胞产生HIV， 导致艾滋病毒的增加干扰了正常的肉芽肿 针对M.结核该提案的具体目标是 阐明结核患者单核细胞的基础， M.结核病有利于艾滋病毒的复制，以及如何扩增病毒和 细胞因子活性影响肺泡细胞损伤和 肉芽肿该提案的具体目标是： 具体目标1：检查增强的 来自HIV血清阴性患者的单核细胞对活动性 从结核病到艾滋病病毒感染。 具体目标2：确定M.结核表达 健康人血液单核细胞和肺泡巨噬细胞的病毒活性 在体外感染艾滋病毒后，以及从艾滋病毒- 感染的人。 具体目标3：检查增强的病毒表达和 由HIV和M. 肺结核对肺泡上皮细胞和非细胞的损害 基质，以及多核巨细胞（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).