Basic Research on the escape mechanism of intracellular parasites and the host response in infection

几种细菌和原生动物寄生虫能够逃避吞噬细胞的细胞内杀伤，并能够在巨噬细胞内繁殖。利用结核分枝杆菌、单核增生李斯特菌、沙门菌、嗜肺军团菌、耶尔森菌、刚地弓形虫和利什曼原虫等细胞内寄生虫，分析了细胞内寄生的分子机制和对这些寄生微生物的免疫反应，特别参考了宿主防御感染的表达。在目前的研究中，可以在某些种类的细菌中鉴定出参与逃避吞噬细胞杀伤的基因和蛋白质。一些内源性细胞因子在巨噬细胞的激活和抗原特异性T细胞依赖性保护性免疫的诱导中起重要作用。在原生动物感染模型中，通过分析热休克蛋白的诱导与保护性免疫表达的关系，进一步了解其防御机制。本项目获得的结果将有助于对宿主-寄生虫关系的最新认识，并可能为将来开发新的抗细胞内寄生虫疫苗铺平道路。

Several bacterial and protozoan parasites are capable of escaping the intracellular killing of phagocytes and able to multiply inside macrophages. Using intracellular parasites including Mycobacterium tuberculosis, Listeria monocytogenes, Salmonella spp., Legionella pneumophila, Yersinia spp., Toxoplasma gondii and Leishmania major, we have attempted to analyze the molecular mechanisms of intracellular prasitism and the immunological responses to those parasitic microorganisms with special reference to the expression of host defense against infection in the host.In the present study, genes and proteins involved in the escape from phagocyte killing could be identified in some species of bacteria. Some kinds of endogenous cytokines were revealed to be important in the activation of macrophages and induction of antigen-specific T cell-dependent protective immunity. In a model of protozoan infection, analysis on the relationship between the induction of heat-shock protein and the expression of protective immunity resulted in the further understanding of the mechanism of defense.The results obtained in this project will be useful in the up-to-date understanding of the host-parasite relationship and may pave the way to the development of novel vaccine against intracellular parasites in the future.