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Clarification of evasion mechanisms of protozoa on the basis of expression pattern of heat shock proteins in parasites and hosts.

根据寄生虫和宿主中热休克蛋白的表达模式阐明原生动物的逃避机制。

基本信息

批准号：
10470067
负责人：
HIMENO Kunisuke
金额：
$ 8万
依托单位：
Tokushima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

Infection is a desperate fight between pathogens and infected hosts, and each side prepares dexterous strategies to endure the attack from the other side. Thus, infection should be stressful both for invading microorganisms and infected hosts. Accordingly, it is conceivable that expression of heat shock proteins (HSPs) is an essential process for both pathogens and host mice. In a series of study using various protozoa which use different mechanisms of evasion from host defense systems, we examined the function of HSPs contributing to the evasion or the host-defense. Following results were obtained by those investigations.1. Contribution of HSP65 to host-defense.1) In mice acquired resistance against some pathogens, γδ, NK or NKT cells, those of which play essential roles in initial stages of host defense against toxoplasma, trypanosoma cruzi and Leishmania major, respectively, express HSP65 in host macrophage and contribute to host-defense. 2) On the other hand, in susceptible mice or mice infected with high virulent strains of protozoa, those protozoa evade host defense systems via preventing the expression of HSP65.2. Contribution of HSP to pathogen-evasion in the case of with Plasmodium yoelii (mouse malaria).1) A low virulent strain of P.yoelii fails to express HSP90 and this strain can not survive within the infected host. 2) On the other hand, a high virulent strain have a potential to express the HSP, then they can survive in the infected host mice. 3) It is noteworthy that the high virulent strain prepare tricky expression mechanisms. That is, they express HSP90 only when they are attacked by host defense systems in resistant mice.It is very important to further elucidate the rule or relationships between the expression of HSPs and parasite-evasion/host defense. This direction of research should provide a direction for development of vaccines for various infections with obligate intracellular pathogens.

感染是病原体和受感染宿主之间的一场绝望的战斗，双方都准备了灵活的策略来抵御对方的攻击。因此，对于入侵的微生物和受感染的宿主来说，感染都应该是有压力的。因此，可以想见，热休克蛋白(HSPs)的表达对病原体和宿主小鼠都是一个必不可少的过程。在使用不同机制逃避宿主防御系统的各种原生动物的一系列研究中，我们研究了热休克蛋白在逃避或宿主防御中的作用。通过这些调查，获得了以下结果：1.热休克蛋白65在宿主防御中的作用1)小鼠对某些病原体γδ、NK或NKT细胞产生抵抗力，这些细胞分别在宿主防御弓形虫、克氏锥虫和大利什曼原虫的初期阶段发挥重要作用，在宿主巨噬细胞中表达热休克蛋白65并参与宿主防御。2)另一方面，在敏感小鼠或感染高毒力原虫株的小鼠中，这些原虫通过阻止HSP65.2的表达来逃避宿主防御系统。热休克蛋白在约氏疟原虫(小鼠疟疾)逃避病原体中的作用1)约氏疟原虫低毒力株不表达HSP90，不能在受感染的宿主内存活。2)另一方面，高毒力菌株具有表达HSP的潜力，因此它们可以在感染的宿主小鼠中存活。3)值得注意的是，高毒力菌株具有复杂的表达机制。也就是说，它们只在抗性小鼠受到寄主防御系统的攻击时才表达HSP90。进一步阐明HSPs的表达与寄生逃避/寄主防御之间的规律或关系是非常重要的。这一研究方向应该为各种专性细胞内病原体感染的疫苗的开发提供方向。