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

细胞内寄生虫逃逸机制及宿主感染反应的基础研究

• 批准号: 07307004
• 负责人: MITSUYAMA Masao
• 金额: $ 5.31万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07307004/
• 关键词: Intracellular parasitism; Bacteria; Protozoa; Macrophages; Infection; Host defense

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.

一些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。使用细胞内寄生虫，包括结核分枝杆菌、单核细胞增生李斯特菌、沙门氏菌，嗜肺军团菌，耶尔森氏菌，弓形虫（Toxoplasma gondii）和硕大利什曼原虫（Leishmania major）的细胞内寄生和免疫应答的分子机制，特别是宿主对感染的防御表达，在本研究中，我们在一些种细菌中鉴定了参与逃避吞噬细胞杀伤的基因和蛋白。某些内源性细胞因子在巨噬细胞活化和诱导抗原特异性T细胞依赖性保护性免疫中起重要作用。在原虫感染模型中，通过分析热休克蛋白的诱导与保护性免疫表达之间的关系，进一步了解了原虫的防御机制，为深入了解宿主-寄生虫关系提供了理论依据，也为今后开发抗胞内寄生虫的新型疫苗奠定了基础。

项目成果

Fujio, H: "Decreased capacity of aged mice to produce interferon-gamma in Legionella pneumophila infection." Mech. Ageing Develop.81. 97-106 (1995)

Fujio, H：“老年小鼠在嗜肺军团菌感染中产生干扰素 γ 的能力下降。”

Fujio, Hironori, et al: "Decreased capacity of aged mice to produce interferon-gamma in Legionella pneumophlla infection." Mech.Aging Dev.81. 97-106 (1995)

Fujio、Hironori 等人：“老年小鼠在肺炎军团菌感染中产生干扰素-γ 的能力下降。”

Song, Fel, et al: "Differential effects of viable and killed bacteria on IL-12 expression of macrophages." J.Immunol.156. 2979-2984 (1996)

Song, Fel 等人：“活细菌和灭活细菌对巨噬细胞 IL-12 表达的不同影响。”

Hisaeda, H., et al: "HSP65 induced by gd T cells prevents apoptosis of macrophages and contributes to host defense in mice infected with Toxoplasma gondii." J.Immunol.(in press). (1997)

Hisaeda, H. 等人：“gd T 细胞诱导的 HSP65 可防止巨噬细胞凋亡，并有助于感染弓形虫的小鼠的宿主防御。”

Arai, T., et al: "Endogenous IL-10 prevents apoptosis in macrophages during Salmonella infection." Biochem.Biophys.Res.Comm.213. 600-607 (1995)

Arai, T. 等人：“内源性 IL-10 可防止沙门氏菌感染期间巨噬细胞凋亡。”