血小板与补体的协同作用在抗白假丝酵母菌系统感染中的作用及机理研究

临床上系统感染常伴随着血小板的激活与减少，及因凝血级联途径和补体系统过度激活引起的脓毒性休克，但这一现象发生的分子机理尚不清楚。新近研究显示，血小板与白假丝酵母菌间存在复合体形成与解聚的动态作用过程，这一过程由补体系统协助完成，且伴随着机体凝血状态的改变。同时体内实验显示血小板缺失的小鼠在感染白假丝酵母菌后成活时间明显缩短。据此，我们提出血小板在补体系统的协同作用下与白假丝酵母菌形成复合体，介导机体免疫清除，而复合体的解聚则导致白假丝酵母菌的免疫逃逸和疾病的发生。申请项目拟通过活体显微成像、流式细胞术和PET-CT等技术，研究血小板与白假丝酵母菌的动态作用机制，阐明该动态作用过程与弥散性血管内凝血等疾病发生的相关性，进一步揭示血小板与补体系统的协同作用在抗白假丝酵母菌系统感染中的作用和分子机理,从而为治疗系统性真菌感染及其所致出凝血疾病提供新思路及潜在干预靶点。

In clinic, systemic infection is often accompanied by activation and decrease of platelets, as well as septic shock caused by over activation of coagulation cascade and complement system. The molecular mechanism of this phenomenon is not clear. Our recent research shows that there is a dynamic process with complex formation and dissociation between platelets and Candida albicans, which is assisted by complement system and accompanied by changes of blood clotting property. Further in vivo experiments show that the survival time was significantly shortened when platelet knock-out mice were infected with C. albicans. We hypothesize that under the synergism of complement system, platelets form complex with C. albicans, which mediates immune clearance, while the depolymerization of the platelet-C. albicans complex leads to fungal immune escape and disease progression. This application project is intended to use living microscope, flow cytometry and PET-CT as the main techniques, study the mechanism of platelet-C. albicans dynamic interaction, clarify the effect of the platelet-C. albicans dynamic process on the pathogenesis of disseminated intravascular coagulation, and further reveal the synergistic effect of platelet and complement on anti-fungal systemic infection. This study is expected to provide a new therapeutic approach and potential target for the better control and treatment of systemic fungal infection and the related coagulation diseases.