猪链球菌表面蛋白SntA与补体C1q互作抑制经典补体激活途径的分子机制

补体逃逸是免疫逃逸的重要机制之一，病原菌的表面蛋白和分泌蛋白可以通过多种机制干预补体的激活。猪链球菌2型（SS2）是一种重要的人兽共患病原菌，其免疫逃逸机制缺乏系统研究。本项目前期研究发现，SntA是SS2的一个含血红素的表面蛋白，能与猪的补体C1qA相互作用。最近的研究发现，血红素可特异性结合C1qA，抑制经典补体激活途径（J Biol Chem. 2011）。因此我们提出了"SntA与C1qA互作是SS2补体逃逸的一种机制，该机制可能与SntA中的血红素分子有关"的假设。项目拟从SntA-C1qA相互作用验证、互作结构域和位点解析、互作对经典补体途径的调控作用等三个方面的研究来回答上述假设，并用已经获得的sntA突变菌株在细菌水平进行验证，揭示SntA介导的猪链球菌补体逃逸的分子机制，对理解猪链球菌免疫逃逸机理，发展新的防治策略和技术具有重要意义。

Complement evasion is one of the most important immune evasion mechanisms. Bacterial surface-bound and excreted proteins can block complement activation through a range of different mechanisms. Streptococcus suis type 2 (SS2) is an important emerging zoonotic bacterium. Its immune evasion mechanism is lack of systemic study. Our previous study found that SntA is a heme-binding surface protein of SS2 which can interact with complement C1qA. Recent study demonstrated that heme can interact with C1qA and inhibit the classical complement pathway (J Biol Chem. 2011, 286(18): 16459-16469). So we suppose that "SntA-C1qA interaction is a complement evasion mechanism of SS2, which may be mediated by the heme in SntA protein". To verify this hypotheses, the following three studies will be carried out: Validation of SntA-C1qA interaction; Characterization of their interact domains and sites; Regulation of the classical complement pathway by SntA-C1qA interaction. Then the sntA mutant SS2 strain will be used to verify the SntA-mediated complement evasion mechanism. This study shall not only provide more scientific data to understand the complement evasion mechanism of SS2, but also contribute to developing novel strategies to prevent and control this important infectious disease.