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Role of heat shock protein expressed on protozoa and hosts

原生动物和宿主表达的热休克蛋白的作用

基本信息

批准号：
04044129
负责人：
HIMENO Kunisuke
金额：
$ 8.26万
依托单位：
Tokushima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-04044129/
关键词：
heat shock protein protozoa protective immunity low and high virulence escape gamma delta T cells HSP65 host macrophage 原虫感染 γδ型T細胞トキソプラズママラリア

项目摘要

Toxoplasma gondii is an obligate intracellular protozoan parasite and a serious pathogen of opportunistic infection in compromised hosts like AIDS. Cellular immunity mediated by T cells plays an essential role in protection against this protozoan infection. Mice readily acquire protective immunity against a low-virulence Beverley strain by immunization with Toxoplasma homogenate while live vaccination with sublethal doses of Beverley strain is required for the protection against infection with a high-virulence RH strain.A 650-kDa heat shock protein (HSP65) was expressed on peritoneal macrophages of BALB/c mice that had been infected with a low-virulence Beverley strain of Toxoplasma gondii or immunized with homogenate of Toxoplasma, as determined by western blot assay using a monoclonal antibody specific for mycobacterial HSP65 and by an immunohistochemical electron microscopy using gold particles. On the other hand, this HSP65 was not expressed when infection had occurred with a high- … More virulence RH strain of T.gondii. HSP65 was, however, expressed even in the infection with RH strain when host mice had acquired resistance against this high-virulence Toxoplasma according to live vaccination with a sublethal dose of Beverley strain. By contrast, when mice were infected with mutant Beverley strain which had acquired high virulence after serial passages into murine peritoneal cavities, these mice lost potentials to express HSP65 on their macrophages. Different from mice, rats are genetically resistant against the infection even with RH strain, and HSP65 was also expressed on their macrophages after infection but not on those of athymic nude rats that are susceptible to such an infection. These results suggest the important role played by HSP65 in developing effective protective immunity against infection with this protozoa in vivo.Athymic nude mice and SCID mice were susceptible to this infection and they did not show an ability to express HSP65 after infection or immunization. Further, BALB/C mice depleted of T cells, especially gd T cells, became susceptible to the infection even with the low-virulence Beverley strain and HSP65 was scarcely expressed on their macrophages. Thus, T cells, especially gd T cells, play an important role in the induction of HSP65 on host macrophages and in acquiring resistance against Toxoplasma infection. Less

弓形虫是一种专性的胞内原生动物寄生虫，是艾滋病等致病宿主机会性感染的严重病原体。T细胞介导的细胞免疫在预防这种原虫感染中起着至关重要的作用。小鼠很容易通过接种弓形虫匀浆获得对低毒力Beverley株的保护性免疫，而需要亚致死剂量的Beverley株活疫苗来保护小鼠免受高毒力RH株的感染。BALB/c小鼠感染低毒力Beverley株或用弓形虫匀浆免疫BALB/c小鼠的腹腔巨噬细胞上表达650 kDa的热休克蛋白(HSP65)，通过使用针对分枝杆菌HSP65的单抗的Western印迹试验和使用金粒子的免疫组织化学电子显微镜检测。另一方面，当发生高…感染时，这种HSP65不表达弓形虫RH株毒力较强。然而，即使在感染RH株的宿主小鼠对这种高毒力弓形虫获得抵抗力时，HSP65也表达，根据贝弗利株的亚致死剂量活疫苗接种。相比之下，当小鼠感染突变的Beverley菌株时，这些小鼠失去了在其巨噬细胞上表达HSP65的能力，该突变菌株在连续传代到小鼠腹膜腔后获得了高毒力。与小鼠不同，大鼠即使感染RH株也具有遗传抵抗力，并且HSP65在感染后的巨噬细胞上也有表达，而在易受这种感染的裸鼠的巨噬细胞上则不表达。这些结果提示HSP65在体内形成对该原虫感染的有效保护性免疫中起重要作用。裸鼠和SCID小鼠对这种感染易感，感染或免疫后均不表现出表达HSP65的能力。此外，耗尽T细胞，尤其是gdT细胞的BALB/C小鼠，即使是低毒力的Beverley株，也变得对感染敏感，并且HSP65在它们的巨噬细胞上几乎不表达。因此，T细胞，尤其是GdT细胞，在宿主巨噬细胞上诱导HSP65和获得对弓形虫感染的抵抗力方面起着重要作用。较少