RESPONSES OF HUMAN LEUKOCYTES TO LIPOARABINOMANNAN

描述（根据申请人的摘要和具体目标改编）： 结核病每年在全世界造成的死亡人数超过 任何其他单一传染病。 目前了解的 结核病的发病机制表明，先天宿主防御决定了 分枝杆菌感染是否导致活动性疾病， 感染被成功控制。 宿主反应旨在限制 分枝杆菌的生长包括白细胞的激活和 肉芽肿的形成。 有效的肉芽肿形成对于 结核病的控制，并开始与周边的迁移 白细胞进入肺部 而趋化细胞因子的产生 受感染的肺泡巨噬细胞可能刺激白细胞 招募，特定分枝杆菌产品对这种反应的影响 尚未确定。 本申请假设， 分枝杆菌细胞壁糖磷脂脂阿拉伯甘露聚糖（LAM） 受感染的肺泡巨噬细胞用于募集外周T细胞， 感染部位，并随后抑制这些 迁移性T细胞 具体目标是：1）对功能进行表征 和表型的白细胞迁移到LAM; 2）以确定一个机制， 白细胞对LAM的趋化反应的基础;以及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.