CYTOKINE-INDEPENDENT DEFENSES AGAINST MYCOBACTERIUM TUBERCULOSIS

针对结核分枝杆菌的独立于细胞因子的防御

• 批准号: 7378037
• 负责人: RICHARD F SILVER
• 金额: $ 0.16万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7378037
• 关键词: CYTOKINE; INDEPENDENT; DEFENSES; AGAINST; MYCOBACTERIUM

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. The overall goal of this protocol is to determine the cytokine-independent mechanisms by which various lymphocyte populations mediate killing of intracellular Mycobacterium tuberculosis (M. tb) within human monocytes and alveolar macrophages. The specific aims are 1) to determine the contact-dependent mechanisms by which lymphocytes activate bactericidal functions of M. tuberculosis-infected mononuclear phagocytes; 2) to determine whether the maximal lymphocyte-mediated activation of M. tuberculosis-infected mononuclear phagocytes requires sequential or interactive effects of cell contact and cytokine production; and 3) to determine whether other lymphocyte subsets (including CD8+ T cells, gamma-delta T cells and natural killer (NK) cells) mediate contact-dependent activation of M. tuberculosis-infected mononuclear phagocytes, to compare the mechanisms used by these effector populations to those of CD4+ T cells, and to determine the role of fas/fasL-mediated cytotoxic effector mechanisms on killing of M. tuberculosis within human mononuclear phagocytes. Our studies are primarily based on an in vitro assay for assessment of intracellular growth of M. tb. We have been able to utilize this assay to demonstrate the ability of lymphocyte populations to mediate killing of intracellular M. tb. Various assays of cytotoxicity and apoptosis have been used to determine the correlation between these lymphocyte functions and killing of M. tb. The participation of human subjects in the study involves both blood drawing and bronchoscopy with bronchoalveolar lavage. Blood monocytes and various lymphocyte populations are isolated from peripheral blood. As M. tb is spread via the respiratory route, the most relevant mononuclear phagocytes for study are alveolar macrophages. Bronchoalveolar lavage is utilized to obtain these cells from healthy non-smokers.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。该方案的总体目标是确定各种淋巴细胞群介导杀死细胞内结核分枝杆菌（M.结核）在人单核细胞和肺泡巨噬细胞内。具体目的是：1）确定淋巴细胞激活M.结核感染的单核吞噬细胞; 2）以确定是否最大的淋巴细胞介导的M.结核感染的单核吞噬细胞需要细胞接触和细胞因子产生的顺序或交互作用;和3）确定其他淋巴细胞亚群（包括CD 8 + T细胞、γ-δ T细胞和自然杀伤（NK）细胞）是否介导M的接触依赖性活化。结核感染的单核吞噬细胞，比较这些效应群体的机制，CD 4 + T细胞，并确定Fas/FasL介导的细胞毒性效应机制的作用，对M.人单核吞噬细胞内的结核病。我们的研究主要是基于一个在体外测定评估的细胞内生长的M。TB.我们已经能够利用该测定来证明淋巴细胞群介导细胞内M. TB.细胞毒性和细胞凋亡的各种测定已被用于确定这些淋巴细胞功能与M. TB.人类受试者参与研究涉及抽血和支气管肺泡灌洗的支气管镜检查。从外周血中分离血液单核细胞和各种淋巴细胞群。作为M.结核病是通过呼吸道传播的，研究中最相关的单核吞噬细胞是肺泡巨噬细胞。支气管肺泡灌洗用于从健康的非吸烟者获得这些细胞。