甲型流感病毒重症感染下C反应蛋白介导的免疫损伤机制研究

甲型流感病毒重症感染时有发生，过度炎症免疫反应是其重要的致病机制。C反应蛋白是一个宿主先天免疫调节因子，我们前期的研究显示C反应蛋白与重症禽流感病毒感染免疫损伤有关，小鼠感染模型研究显示控制C反应蛋白水平可降低H1N1(PR8)对小鼠的致病性和致死性。而关于重症流感病毒感染下C反应蛋白介导的免疫损伤机制尚不清楚。 本研究拟通过人CRP转基因小鼠和CRP基因敲除小鼠感染模型来研究甲型流感病毒重症感染下C反应蛋白介导的免疫损伤机制，识别其免疫调节路径中的潜在可控关键分子，并通过免疫细胞和肺组织共培养感染模型，结合RNA干扰技术，探究CRP免疫调节路径中可调控分子潜在应用价值，为甲型流感病毒重症感染的防控提供相关理论依据和研究基础。

Influena A virus has caused severe infection frequently. Over imflamatory response is a key pathogenesis in severe influenza A infection. C reactive protein (CRP), a mediator of host innate immune, was suggested to be related with immunopathological damage in servere patients infected by avian influenza viruses. Mouse model demonstrated that management of CRP level reduced the morbility and mortality caused by H1N1 (PR8) infection. However, it is unknown about the mechanism of immunopathological damage mediated by CRP in influenza A severe infection. To provide a theoretical principle and reference for control and prevention of severe influenza A infection, in this study, we will try to figure out the mechanism through the methods of mouse infection model using Human CRP knock in mouse and CRP knock out mouse, and try to identify those controllable key mollecular in the pathway of CRP mediation through RNA interference techology and coculture model with immune cells and lung tissues.