Effects of Trehalose Dimycolate on Macrophage Signaling

海藻糖二霉菌酸酯对巨噬细胞信号传导的影响

• 批准号: 6938330
• 负责人: Kaori Sakamoto
• 金额: $ 5.54万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6938330
• 关键词: Mycobacterium tuberculosis; anergy; bacterial toxins; biological signal transduction; chemical structure function; confocal scanning microscopy; enzyme linked immunosorbent assay; gel mobility shift assay; glycolipids; host organism interaction; interferon gamma; macrophage; microarray technology; polymerase chain reaction; transfection; trehalose; tuberculosis; western blottings

DESCRIPTION (provided by applicant): Although IFN-gamma-activated macrophages are capable of destroying mycobacteria, most macrophages within a tuberculoid granuloma are maintained in an anergic state. Understanding the mechanism of macrophage anergy will allow development of both preventative and curative strategies for the-treatment of tuberculosis and other mycobacterial diseases. The hypothesis to be tested is that trehalose dimycolate (TDM), a prominent component of the mycobacterial cell wall, actively interferes with IFN-gamma signaling and is an important mechanism by which these bacilli modulate macrophage behavior. The specific aims of this proposal are: 1. To identify the macrophage receptor for TDM or the mechanism by which TDM triggers macrophage signaling, and determine how the mode of TDM presentation affects this process. 2. To dissect the TDM proinflammatory signaling pathway in the macrophage and determine how this pathway subverts the IFN-gamma signaling pathway. Techniques to be employed during this study include: enzyme-linked immunosorbent assay, electron mobility shift assay, quantitative real-time polymerase chain reaction, immunoblot, affinity isolation, microarray analysis, transfection, confocal microscopy, and lipid raft analysis.

描述（由申请人提供）：虽然IFN-γ激活的巨噬细胞能够破坏分枝杆菌，但结核样肉芽肿内的大多数巨噬细胞仍维持在无能状态。 了解巨噬细胞无反应性的机制将有助于制定治疗结核病和其他分枝杆菌疾病的预防和治疗策略。待检验的假设是海藻糖二霉菌酸酯 (TDM) 是分枝杆菌细胞壁的重要组成部分，它会主动干扰 IFN-γ 信号传导，并且是这些杆菌调节巨噬细胞行为的重要机制。 该提案的具体目标是： 1. 鉴定TDM的巨噬细胞受体或TDM触发巨噬细胞信号传导的机制，并确定TDM呈递模式如何影响这一过程。 2. 剖析巨噬细胞中的TDM促炎信号通路，并确定该通路如何破坏IFN-gamma信号通路。 本研究中使用的技术包括：酶联免疫吸附测定、电子迁移率测定、定量实时聚合酶链反应、免疫印迹、亲和分离、微阵列分析、转染、共聚焦显微镜和脂筏分析。