猪肺炎支原体EF-Tu劫持H因子逃避宿主补体旁路途径激活机制研究

猪肺炎支原体（Mycoplasma hyopneumoniae, Mhp）感染机体后持续存在，其免疫逃避的机制尚不清楚。能否有效抑制补体旁路途径的激活是感染早期病原免疫逃逸的关键之一。申请人前期研究发现Mhp表面蛋白EF-Tu (elongation factor thermo unstable) 可以结合补体活化的关键负反馈调节组分H因子，且定植能力更强的强毒株EF-Tu表达量更高。提示EF-Tu可能通过劫持H因子介导Mhp的免疫逃避。本申请拟以此为基础，利用分段表达与同源建模分析EF-Tu与H因子的结合方式及关键位点；从体内与体外两个角度，分别比较封闭或高表达EF-Tu的Mhp菌株通过结合H因子对补体活化的影响，明确Mhp的EF-Tu表达量与宿主补体活化的抑制的关联性。解析在Mhp感染中EF-Tu募集H因子逃避宿主补体清除的机理。为Mhp的致病机制及抗感染药物的研发提供理论依据。

Mycoplasma hyopneumoniae (Mhp) is an important pathogen surviving long time in the host without being cleared. But its mechanism of evasion of the host immune system is not clear. The ability to effectively inhibit the complement activation of alternative pathway is the key to immune evasion for pathogen in early infection. Our previous study showed that the surface protein EF-Tu (elongation factor thermo unstable) had stronger ability to combine factor H, the negative feedback regulator of the complement activation pathway. And the expression level of EF-Tu in virulent Mhp strain with stronger colonization ability was significantly higher than that of the attenuated strain, suggesting that EF-Tu may be involved in the Mhp evasion of complement activation guided by factor H. The present study is intended to identify the key binding region of EF-Tu and factor H and verify the relation of the expression of EF-Tu and the inhibition of host complement activation, and elucidate the mechanism of EF-Tu recruiting factor H to evade host complement clearance during Mhp infection.