沙眼衣原体感染对MICA*A5.1分子、Treg细胞的影响及机制研究

Chlamydia trachomatis is an important pathogen of sexually transmitted disease, the interaction between Ct and host cells is the focus of Ct pathogenesis research. Our preliminary work found that: ①Ct infection could down regulate the expression of MICA molecules on the host cell surface, and this effect is related to the genotype of the MICA. The MICA*A5.1 gene positive host cells can resist the down regulation after Ct infection and enhance the cytotoxic activity of NK cells. ②MICA*A5.1 gene was negatively correlated with Ct infection but had no protective effect on Ct infection complications. ③The Treg cells reduced in MICA*A5.1 gene positive Ct infected persons. Based on these findings, we speculate that: the MICA*A5.1 molecule can resist the down regulation during Ct infection and activate NK cells by NKG2D pathway. This will promote NK killing of Ct infected cells and Treg cells. So we intend to further clarify by flow cytometry, Western blot, ELISA and so on. ①The time-effect in Ct regulation of the MICA molecule and the relationship with MICA genotypes; ②The killing activity of NK cells on different MICA genotype Ct infection cells and Treg cells; ③The status of the Treg cells and the NK inhibitory effect on Treg cells in different MICA genotypes Ct infected persons. This study will provide new experimental evidence to the pathogenic mechanism of Ct infection.

沙眼衣原体是引起性传播疾病的重要病原体，Ct与宿主细胞的相互作用是其致病机制的研究重点。我们前期发现：①MICA*A5.1分子能抵抗Ct的下调，并增强NK细胞对Ct感染细胞的杀伤；②MICA*A5.1基因与Ct感染负相关但与感染后并发症无关；③MICA*A5.1基因阳性的Ct感染者体内Treg细胞减少。据此我们认为：MICA*A5.1分子可抵抗Ct感染后的下调，并通过NKG2D途径活化NK细胞，在促进NK杀伤Ct感染细胞的同时也促进NK对Treg的杀伤和抑制。基于上述假设，我们拟通过流式细胞术、免疫印迹、ELISA等策略进一步明确：①Ct下调MICA分子的时效关系及其与MICA基因型的关系；②NK细胞对Ct感染的不同MICA基因型细胞以及Treg细胞杀伤活性的差异；③不同MICA基因型Ct感染者体内Treg的状态，及体内NK对Treg的抑制效应。本课题将为Ct致病机制研究提供新的实验证据。

沙眼衣原体（Chlamydia trachomatis, Ct）是一类重要的胞内病原体，我们先期发现沙眼衣原体感染后可下调宿主细胞表面的MICA分子。在此基础上本项目研究了Ct感染对MICA分子的下调作用与宿主细胞MICA*A5.1基因型的关系；NK细胞对Ct感染的不同MICA*A5.1基因型细胞的杀伤活性；比较不同MICA*A5.1基因型Ct感染者体内Treg细胞数量及相关细胞因子的差异；并进一步探讨不同MICA*A5.1基因型Ct感染者的NK细胞对Treg细胞杀伤活性的差异。结果发现：①沙眼衣原体感染后可下调MICA*A5.1阴性宿主细胞的MICA蛋白的表达；②NK细胞对沙眼衣原体感染的MICA*A5.1阳性宿主细胞的杀伤作用明显强于MICA*A5.1阴性宿主细胞；③MICA*A5.1阳性Ct感染者外周血中CD4+CD25+Treg细胞数量及血清中IL-10和TGF-β的含量均低于MICA*A5.1阴性的Ct感染者；④MICA*A5.1阳性Ct感染者的NK细胞对CD4+CD25+Treg细胞的杀伤效应强于MICA*A5.1阴性的Ct感染者。以上结果提示：MICA*A5.1分子可抵抗Ct感染后的下调作用，并促进NK细胞对宿主细胞以及Treg细胞的杀伤，在促进清除病原体的同时也可能导致炎症迁延。该研究结果阐明了MICA*A5.1基因多态性与沙眼衣原体感染之间的关系，进一步揭示了沙眼衣原体与宿主相互作用的复杂性。