菲氏军团菌是革兰阴性胞内菌，可引起军团病，但其胞内增殖及致病机制尚未阐明。我们前期研究发现，菲氏军团菌可在宿主细胞内繁殖并诱导细胞因子释放及细胞死亡。已有研究证实，DotA蛋白能够调节军团菌的胞内增殖及引起宿主细胞炎症反应。基于当前研究现状及军团菌属同源性，我们推断: 1.菲氏军团菌利用DotA蛋白募集宿主蛋白在细胞内增殖。2.菲氏军团菌依赖DotA蛋白将鞭毛蛋白转运至胞质，调节活化caspase-1，诱导炎性细胞因子释放和焦亡，引起炎症反应。本研究拟以野生型与dotA基因缺陷型菲氏军团菌感染宿主细胞，探究其胞内增殖机制，结合野生型及caspase-1基因缺陷型小鼠巨噬细胞及小鼠感染实验，分析DotA蛋白转运鞭毛蛋白进入宿主细胞后，诱发宿主炎症性反应的过程，揭示菲氏军团菌引起呼吸系统疾病的本质，对解析军团菌及其它胞内菌引起人类呼吸系统炎症反应的致病机理提供可靠理论基础。

Legionella feeleii is a Gram-negative intracellular bacterium, which caused Legionnaires disease. However, the mechanisms of the bacterial intracellular growth and pathogenesis are still not clear. In our previous researches, we found that L. feeleii could proliferate in host cells, induced cytokines secretion and caused the cells death. It has been demonstrated that DotA protein could mediate the intracellular proliferation of Legionella strains and cause the inflammatory reaction of host cells. Based on the current researches and the homology of Legionellae, we inferred: 1. In order to proliferate in the host cells, L. feeleii could utilize DotA protein to recruit the protein of the host cells. 2. L. feeleii could translocate the flagellin via DotA protein into the cytoplasm, active caspase-1 and induce cytokines secretion and pyroptosis. In this study, we will make L. feeleii dotA mutant, and try to investigate the mechanism of bacterial proliferation via infection of the mammalian cells. In combination of infection experiments that are performed in vitro and in vivo, the process of bacterial flagellin that was translocated into the cytoplasma and induction of inflammation will be analyzed. This research will elucidate the mechanisms of L. feeleii infection and the pathogenesis of L. feeleii caused respiratory diseases. This project will provide reliable theoretical basis for analyzing human respiratory system inflammation that caused by Legionella and other intracellular bacteria.