结核菌感染上调CD157表达的分子机制及其对中性粒细胞/单核细胞迁移功能的影响

中性粒细胞/单核细胞在组织中浸润是结核病发生的早期事件，在结核病发生中起重要作用。CD157在中性粒细胞/单核细胞组织浸润过程中起不可缺少的作用，具体涉及形态改变、黏附、跨内皮迁移和趋化作用。我们研究发现:与健康对照和结核菌潜伏感染者相比，结核患者外周血CD157表达水平显著增高，并随着抗痨治疗后，逐渐下降至健康者水平；CD157在结核菌感染组织中富集，其水平与浸润的单核细胞数量正相关；体外研究发现，结核菌上调单核细胞表面CD157的表达，此过程受IFNγ的影响。本项目拟通过探讨1）CD157对中性粒细胞/单核细胞向结核感染组织迁移功能的影响；2）结核菌与细胞模式受体的直接作用在上调CD157表达的作用和分子机制；3）结核菌诱导的细胞因子和趋化因子对CD157表达的影响，系统地阐明结核菌感染上调CD157表达的分子机制及其作用，为CD157在结核病诊断、治疗和疫苗研发中的应用提供科学依据。

The accumulation of neutrophil and mononcyte in the organization is the early response to mycobacterial infection, which is important in the pathogenesis of TB. CD157 is the crucial aspect of neutrophil and mononcyte accumulation , including the mediation of modification, adhesion, transendothelial migration and chemotaxis. Our previous studies showed that the expression of CD157 in TB was higher than in healthy donor and latent TB. After anti-TB therapy, its expression could decrease to the normal level.In addition, it highly expressed in the infected organization. In vitro, Mycobacterium tuberculosis directly induced CD157 expression in TB , which IFNγ was involved in. In this project, we will indentify 1) the role of CD157 in neutrophil and monocyte migration; 2) the role and mechanism of Mycobacterium tuberculosis in CD157 expression, when Mycobacterium tuberculosis directly response to the receptor of neutrophils and monocytes; 3) the role and mechanism of cytokines and chemokines , which are induced by Mycobacterium tuberculosis, in CD157 expression. After then, we could clearly identify the mechanism of mycobacterium tuberculosis enhanced expression of CD157 on neutrophils and monocytes and the function of CD157 in TB. This study will provide scientific theory of the application of CD157 in diagnosis, therapy and vaccine development of TB.