CD157调控巨噬细胞功能增强宿主抗结核免疫的作用机制

宿主抗结核免疫是决定结核感染是否发病的关键，但其调控机制尚不清楚。我们前期发现结核患者单核巨噬细胞CD157高表达，CD157表达水平与结核病发生发展密切相关。与野生型小鼠相比，CD157基因敲除小鼠肺部结核菌含量显著增多，病理损害显著加重，表明CD157具有增强宿主抗结核免疫的作用。那么，CD157增强宿主抗结核免疫的具体机制如何？体外结核感染模型证实，CD157可以直接增强巨噬细胞清除结核菌的能力，并上调巨噬细胞炎症因子的分泌。据此，我们提出假说：CD157通过增强巨噬细胞杀菌和炎症因子分泌能力，从而增强宿主固有和获得性抗结核免疫。本项目围绕上述假说，进一步阐明CD157增强巨噬细胞直接杀菌能力和炎症因子表达的具体机制，探讨CD157调控巨噬细胞功能对于T细胞免疫的影响和机制，深入揭示CD157调控宿主抗结核免疫的机制，为基于宿主基因定向治疗结核病策略提供潜在新靶点和科学依据。

The result of infected of mycobacterium tuberculosis (MTB) depends on the host immunity, however, the mechanism of host immunity against mycobacterium tuberculosis still not clear. Our previously data showed that CD157 highly expressed in macrophages in the blood from patients with TB, and the level of CD157 expression was highly related with the occurrence and development of TB. What was more, the CFU was higher in CD157 knockout mouse as well as pathology was more serious comparing with WT mouse. It showed that CD157 could enhance the host immunity against MTB. But it is not clear that how CD157 enhanced the host immunity. In vitro, we found that CD157 could enhance the bactericidal ability and the function of secreting inflammatory cytokines of macrophage. Based on these results, we hypotheses that CD157 could enhance the host innate and acquired immunity against MTB by enhancing the ability of bactericidal and secreting cytokines of macrophage. The project will further study the mechanism of CD157 enhanced the ability of bactericide and inflammatory cytokines expression of macrophage. After then we could explore the impact and mechanism of CD157 regulated T cell immunity by controlled the function of macrophage. This project is expected to reveal the mechanism of CD157 regulating tuberculosis immunity and provide a theory for CD157 as a target for host directed therapy.