生殖支原体经CyPA抑制T细胞活化、调控炎症反应与细胞凋亡

生殖支原体（Mg）是一种能引起泌尿生殖道感染的原核细胞型微生物。课题组前期研究表明人尿道上皮细胞膜上的亲环素（CyPA）是Mg黏附蛋白（MgPa）的受体，能介导Mg黏附或侵入细胞内。CyPA是免疫抑制剂环孢素A的受体，且在调控炎症反应和细胞凋亡等方面发挥重要作用。Mg感染宿主后对宿主的免疫抑制与炎症反应的调控机制尚未阐明。本课题拟采用免疫共沉淀等检测Mg与CyPA互作而抑制T细胞活化，确定其功能域与关键氨基酸；用基因突变和GST-pull down等方法检测Mg诱导人尿道上皮细胞分泌胞外CyPA对促炎症因子、中性粒细胞趋化活性与细胞凋亡的调控及其信号通路；并用CyPA过表达和基因缺陷小鼠从动物水平验证CyPA对Mg感染小鼠T细胞抑制、炎症反应和细胞凋亡的调控，以阐明Mg感染宿主后对宿主的免疫抑制与致病性及其机制，为利用CyPA或其拮抗分子作为靶点开发新型靶向药物与基因工程疫苗奠定实验基础。

Mycoplasma genitalium is a kind of prokaryotic microorganism that can cause urogenital tract infection. Our previous studies showed that the cyclophilin(CyPA) located on the membrane of human uroepithelial cells is the receptor of M. genitalium protein of adhesion (MgPa), which can mediate M. genitalium adhesing or invasing into cells. CyPA is the receptor of the immunosuppressant cyclosporine A, which plays an important role in regulating inflammatory response and cell apoptosis. The regulatory mechanism of immunosuppression and inflammatory response of M. genitalium to host have not been elucidated so far. This study intends to detect that M. genitalium inhibits the activation of T cells by CyPA using co immunoprecipitation, and determine the domain and key amino acids of CyPA；M. genitalium induces human uroepithelial cells to secret CyPA and regulate proinflammatory cytokines, neutrophil chemotaxis and apoptosis, and the corresponding signal transduction pathways will be detected by constructing mutant and GST-pull down and so on. And the effect of CyPA on the inhibition of T cell activation, inflammatory response and cell apoptosis of M.genitalium infected mice will be verified by animal experiments using CyPA overexpressed and gene deficient mice. In order to elucidate the immunosuppressive mechanism of M.genitalium to host, understand the possible pathogenicity and pathogenesis of M.genitalium, and provide new ideas for developing new targeted drugs and genetic engineering vaccines using CyPA or its antagonistic molecules as targets.