Mechanisms by which M. tuberculosis 13KDa lectin modulates human immune responses

结核分枝杆菌13kda凝集素调节人体免疫反应的机制项目概述结核分枝杆菌新蛋白的研究可能是改善结核病（TB）诊断工具、治疗和免疫预防的关键一步，结核病是世界上最流行的传染病之一。我们已经从结核分枝杆菌中鉴定出一种13 KDa的蓖麻蛋白样凝集素，该凝集素可以凝集红细胞并诱导巨噬细胞表达细胞因子。此外，活动性肺结核患者的血清中含有高水平的抗这种凝集素的IgG。在本提案中，我们的目的是表征13 KDa Mtb凝集素在人体免疫反应中的作用。该研究的具体目的是：1)表征由13kda Mtb凝集素引起的先天免疫反应谱；2)测定人APC上表达的参与13kda Mtb凝集素识别的先天受体；3)探讨13kda Mtb凝集素在人APC感染/吞噬结核分枝杆菌过程中的作用；4)检测结核病患者在抗生素治疗前后对13kda Mtb凝集素的特异性体液和细胞免疫反应。我们的长期目标是确定13 KDa Mtb蓖麻样凝集素是否在调节人对TB的免疫反应中发挥作用，重点关注其在控制APC功能中的可能活性。这些研究可能对揭示结核病免疫治疗的新靶点具有重要意义。公共卫生相关性：结核分枝杆菌13kda凝集素调节人类免疫反应的机制项目叙述该项目的发展可能会影响人类健康，因为了解分枝杆菌与人类细胞之间的相互作用对于揭示结核病免疫治疗的新靶点以及疾病生物标志物非常重要。

DESCRIPTION (provided by applicant): Mechanisms by which M. tuberculosis 13 kDa lectin modulates human immune responses Project Summary Study of novel proteins from Mycobacterium tuberculosis may be a critical step for improving diagnostic tools, therapies and immunoprophylaxis against tuberculosis (TB), one of the most prevalent infectious diseases wordwide. We have identified a 13 KDa ricin-like lectin from M. tuberculosis that was found to agglutinate red blood cells and induce cytokine expression by macrophages. Moreover, serum from active tuberculosis patients contained high levels of IgG against this lectin. In the present proposal, we aim to characterize the role of 13 KDa Mtb lectin on human immune responses. The specific aims of the study are to 1) characterize the innate immune response profile elicited by the 13 KDa Mtb lectin; 2) determine innate receptor(s) expressed on human APC involved in the recognition of 13 KDa Mtb lectin; 3) investigate the role of 13 KDa Mtb lectin in the infection/phagocytosis process of M. tuberculosis by human APC and 4) examine specific humoral and cellular immune responses against 13 KDa Mtb lectin in TB patients before and after antibiotic treatment. Our long-term goal is to determine whether 13 KDa Mtb ricin-like lectin plays a role in regulating human immune responses to TB focusing on it possible activity in controlling APC function. These studies could be important in revealing a new target for immunotherapy of tuberculosis. PUBLIC HEALTH RELEVANCE: Mechanisms by which M. tuberculosis 13 kDa lectin modulates human immune responses Project Narrative Development of this project may impact human health because understanding of interactions between Mycobacteria and human cells could be important in revealing novel targets for immunotherapy of tuberculosis as well as disease biomarkers.