Effects of Trehalose Dimycolate on Macrophage Signaling

描述（由申请人提供）：尽管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维持在无能状态。了解巨噬细胞能量的机制将有助于制定预防和治疗结核病和其他分枝杆菌疾病的策略。需要验证的假设是，海藻糖二mycolate （TDM）是分枝杆菌细胞壁的重要成分，可积极干扰ifn - γ信号，是这些杆菌调节巨噬细胞行为的重要机制。

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.