虫媒与病原体：蜱虫的固有免疫信号通路与蜱虫抗细菌感染机制的研究

蜱虫能成为众多病原体的中间宿主，其自身强大的抗感染能力是一个重要原因。本项目将首次研究蜱的固有免疫信号通路，及其在抗细菌感染中的作用。我们发现在蜱中也存在多条固有免疫信号通路，并证明了蜱的JAK-STAT通路对蜱感染人粒细胞埃立克体病病原体Anaplasma具有抑制作用。抑制蜱唾液腺中一类编码5.3kd抗菌肽的基因与蜱的STAT基因，对细菌感染有一致的表型。本项目将在这些前期数据的基础上，深入研究蜱的JAK-STAT信号通路在蜱感染细菌过程中的作用，并探讨蜱转录因子STAT与编码5.3kd抗菌肽基因之间的调控关系。我们将通过蜱活体RNA干扰、转录因子-DNA相互作用、"蜱-病原体-小鼠"感染模型等技术手段，揭示蜱的固有免疫信号通路及其下游效应分子在蜱感染和传播病原体过程中的作用。本项目将通过阐释蜱虫的抗感染机制，为我们研究人类如何更有效抵抗蜱传病原体感染提供一些借鉴。

Recently, Tick-borne diseases in China have attracted wide attention. Ticks carry a large number of pathogens; some of them can infect human beings and cause lethal diseases. As the natural vector for those pathogens, ticks show powerful anti-infection ability but the detail information for tick immune system remain largely unknown. In this project, we study the innate immune signaling pathway in Ixodes ticks and their roles in pathogen infection. We have found that there are three innate immune signaling pathway in ticks, which are Toll, Imd and JAK-STAT pathway. Tick JAK-STAT pathway was found critical for the infection of Anaplasma, the pathogen of human granulocytic ehrlichiosis. We also found the 5.3kd salivary gland protein, which supposed to be a family of anti-microbial peptide, shown similar function with STAT upon Anaplasma infection. Based on these data, we will further characterize the detail function of tick JAK-STAT signaling pathway during pathogen infection, and investigate the links between tick transcriptional factor STAT and genes encoding 5.3kd anti-microbial peptides. The method of in vivo RNAi, protein-DNA interaction, and tick-pathogen-mouse model will be used in this study. The details of tick JAK-STAT pathway and their downstream factors will be characterized and their roles during tick-borne pathogen infection will be illustrated. This will be the first time in China to study the innate immune pathway in ticks, and will help us to understand the unique mechanisms for tick anti-bacterial infection. And this will further contribute to the design of new drugs for prevention and control of tick-borne diseases in China.