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

感染是病原体和受感染宿主之间的殊死搏斗，每一方都准备了灵巧的策略来忍受另一方的攻击。因此，感染对入侵的微生物和被感染的宿主都是有压力的。因此，可以想象，热休克蛋白（HSP）的表达是病原体和宿主小鼠的一个重要过程。在一系列的研究中，我们使用不同的原生动物，使用不同的机制逃避宿主防御系统，检查热休克蛋白的功能有助于逃避或宿主防御。通过这些研究，获得了以下结果：1. HSP 65在宿主防御中的作用：1）在获得性免疫小鼠中，γδ细胞、NK细胞和NKT细胞分别在宿主防御弓形虫、克氏锥虫和硕大利什曼原虫的初始阶段起重要作用，它们在宿主巨噬细胞中表达HSP 65，参与宿主防御。2)另一方面，在易感小鼠或感染高毒力原虫株的小鼠中，这些原虫通过抑制HSP 65.2的表达来逃避宿主防御系统。约氏疟原虫（Plasmodium yoelii，鼠疟）中HSP对病原逃避的贡献1）约氏疟原虫的一个弱毒株不表达HSP 90，该毒株不能在感染的宿主中存活。2)另一方面，高毒力的菌株具有表达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，高毒力菌株制备棘手的表达机制。因此，进一步阐明HSP 90的表达与避虫/宿主防御的关系及规律具有重要意义。这一研究方向应该为开发针对专性细胞内病原体的各种感染的疫苗提供方向。

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.