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Escape mechanisms of intracellular bacteria and the analysis of protective immunity and tissue damage in the infected host

胞内细菌的逃逸机制及感染宿主的保护性免疫和组织损伤分析

基本信息

批准号：
05454190
负责人：
MITSUYAMA Masao
金额：
$ 3.97万
依托单位：
Niigata University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

项目摘要

One of the purpose of this study was to study the escape mechanisms of intracellular bacteria and its contribution to the induction of cell-mediated immunity (CMI) in infected hosts. In addition, we wanted to segregate the protective T cells and those involved in tissue damage with respect to T cell function and antigen in recognition. The following results were obtained in the experiments using murine models of infection.1. LLO (listeriolysin O) encoded by hlya plays a crucial role in the escape of Listeria monocytogenes. LLO is capable of inducing various cytokines in macrophages in addition to its primary effect on cell membrane. 2. Only those strain of Listeria capable of expressing hlya induce CMI.LLO appeared to induce the functional development of T cells through its ability to induce IL-1alpha and IFN-gamma in the host. 3. Protective immunity is exerted by Th1 type CD4^+ T cells by producing a qreat amout of IFN-gamma in an antigen-specific manner. CD4^+ T cells with poor ability to produce IFN-gamma were only active in expression of delayd-type hypersensitivity. 4. Protective T cells recognize a wide range of antigens in L.monocytogenes, while BCG-reactive IFN-gamma-producing CD4^+ T cells recognize mainly 18 to 20kDa antigen. Peripheral blood lymphocytes from tuberculous patients showed a good response against this particular antigen resulting in IFN-gamma production. 5. CD8^+ T cells generated in L.monocytogenes-infected host seemed to contribute to tissue damage through production of TNF.6. Among various cytokines which are non-specifically produced in infected host, NK cell-derived IFN-gamma was critically important in the expression of iNOS (inducible NOS) and was unique to viable bacterial infection.

本研究的目的之一是研究细胞内细菌的逃逸机制及其在感染宿主细胞介导免疫（CMI）诱导中的作用。此外，我们想分离保护性T细胞和那些参与组织损伤的T细胞功能和抗原识别。在使用感染的鼠模型的实验中获得了以下结果。由hlya编码的LLO（溶血素O）在单核细胞增生李斯特菌的逃逸中起着至关重要的作用。LLO除了对细胞膜的主要作用外，还能够诱导巨噬细胞中的各种细胞因子。2.只有那些能够表达hlya的李斯特菌菌株才能诱导CMI。LLO似乎通过其在宿主中诱导IL-1 α和IFN-γ的能力来诱导T细胞的功能发育。3. Th 1型CD 4 ^+ T细胞通过以抗原特异性方式产生大量IFN-γ来发挥保护性免疫。产生IFN-γ能力差的CD 4 ^+ T细胞仅在迟发型超敏反应中表现活跃。4.保护性T细胞识别单核细胞增生李斯特菌中的广泛抗原，而BCG反应性IFN-γ产生的CD 4 ^+ T细胞主要识别18至20 kDa的抗原。来自结核患者的外周血淋巴细胞对这种特定抗原表现出良好的反应，导致IFN-γ产生。5.单核细胞增生李斯特菌感染宿主体内产生的CD 8 ^+ T细胞似乎通过产生TNF而导致组织损伤。在感染宿主中非特异性产生的各种细胞因子中，NK细胞衍生的IFN-γ在iNOS（诱导型NOS）的表达中至关重要，并且是活细菌感染所特有的。