RESPONSES OF HUMAN LEUKOCYTES TO LIPOARABINOMANNAN

描述(根据申请者的抽象和具体目标改编)： 全球每年死于结核病的人数超过 任何其他单一传染病。目前对该问题的理解 结核病的发病机制表明，固有的宿主防御决定了 分枝杆菌感染是否会导致活动性疾病，或者 感染得到了成功的控制。主机响应旨在限制 分枝杆菌的生长包括白细胞的激活和 肉芽肿的配方。有效的肉芽肿形成对 结核病的控制，从外周细胞的迁移开始 白血球进入肺部。而趋化细胞因子的产生 被感染的肺泡巨噬细胞可能刺激白细胞 募集，特定分枝杆菌产品对这一反应的影响 尚未确定。此应用程序假设 分枝杆菌胞壁糖磷脂阿拉伯甘露聚糖(LAM) 受感染的肺泡巨噬细胞可将外周T细胞募集到 感染部位，并随后抑制这些基因的激活 迁移中的T细胞。具体目标是：1)表征功能 和向LAM迁移的白细胞的表型；2)定义一种机制 白细胞对LAM趋化反应的基础；3)确定 LAM抑制白细胞活化的分子基础。

DESCRIPTION (Adapted from applicant's abstract and specific aims): Tuberculosis is responsible for more human deaths worldwide each year than any other single infectious disease. Current understanding of the pathogenesis of tuberculosis suggests that innate host defenses determine whether mycobacterial infection results in active disease or whether the infection is successfully contained. Host responses designed to limit mycobacterial growth include the activation of leukocytes and the formulation of granulomas. Effective granuloma formation is critical for the control of tuberculosis, and begins with the migration of peripheral leukocytes to the lung. While the production of chemoattractant cytokines by infected alveolar macrophages is likely to stimulate leukocyte recruitment, the effect of specific mycobacterial products on this response has yet to be determined. This application hypothesizes that the release of the mycobacterial cell wall glycophospholipid lipoarabinomannan (LAM) from infected alveolar macrophages serves to recruit peripheral T cells to the site of infection, and subsequently suppress the activation of these migrating T cells. The specific aims are: 1) to characterize the function and phenotype of leukocytes which migrate to LAM; 2) to define a mechanistic basis for the chemotactic response of leukocytes to LAM; and 3) to determine the molecular basis for suppression of leukocyte activation by LAM.