猪链球菌2型CSP蛋白抑制猪中性粒细胞胞外诱捕网形成的分子机制

Streptococcus suis serotype 2 (SS2) is one of the most important zoonotic pathogens causing septicemia and Toxic Shock Syndrome in pigs and human beings. Previous research demonstrated that SS2 could inhibit neutrophil extracellular traps (NETs) formation in swine to evade being killed by immune system. The ability of NETs formation was enhanced when a cell surface protein gene (csp) of SS2 was disrupted by transposon insertion. This result demonstrates that CSP protein plays an important role in the inhibition of NETs formation. However, the molecular mechanism remain unclear. In this study, both transposon mutagenesis and NETs quantitative technique are used to identify novel SS2 virulence factors which could suppress NETs formation. Some biological characters such as biofilm and capsule are analysis when csp genes is disrupted. Screening for neutrophil protein interacting with CSP and evaluating the influence of these interaction on NETs formation. Identifying the key signaling pathway responsible for CSP-inducing NETs inhibition. Evaluating the function of CSP protein in NETs formation and bacteremia in SS2-infected pigs. The results of above studies will explain the molecular mechanism of CSP-inducing NETs inhibition which will be benefit for illustrating the pathogenesis of SS2.

猪链球菌2型（SS2）是一种重要的人兽共患病病原，引起猪败血症和人中毒性休克综合征。前期研究发现，SS2能抑制猪中性粒细胞形成胞外诱捕网（NETs）而逃避免疫，且SS2的CSP蛋白基因转座子突变株诱导中性粒细胞形成NETs的能力显著增强，显示CSP在SS2抑制NETs形成的过程中起重要作用，但机制不明。本研究以SS2强毒株ZY05719为研究对象，利用转座子诱变技术，鉴定SS2与抑制中性粒细胞形成NETs相关的毒力因子。在此基础上，分析CSP、新鉴定毒力因子对SS2生物被膜、荚膜等生物学特性的影响；筛选其与中性粒细胞的互作蛋白，评价互作对NETs形成的影响；鉴定CSP蛋白抑制中性粒细胞形成NETs的关键信号通路；评价CSP对SS2在猪体内诱导NETs形成以及产生高菌血症的作用。研究结果将解析猪链球菌2型CSP蛋白抑制NETs形成的分子机制，有助于进一步阐明SS2的致病机理。

猪链球菌2型（SS2）是一种重要的人兽共患病病原，引起猪败血症和人中毒性休克综合征。本项目以SS2强毒株ZY05719为研究对象，利用转座子诱变技术和NETs定量检测技术，鉴定SS2抑制猪中性粒细胞NETs形成的毒力因子。在此基础上，分析CSP蛋白等毒力因子对SS2生物被膜、荚膜和细菌聚集性等生物学特性的影响，以及对NETs形成的影响；筛选CSP与猪中性粒细胞的互作蛋白；比较SS2亲本株和CSP基因缺失株诱导猪中性粒细胞形成NETs的信号通路，鉴定CSP蛋白抑制猪中性粒细胞形成NETs的关键信号通路；检测调控NETs形成相关的细胞因子，阐明了CSP蛋白抑制猪中性粒细胞NETs形成的分子机制，为进一步阐明SS2逃避宿主先天性免疫的机理以及新型药物的开发提供理论依据。