Role of Heat Shock Protein against Protozoan Infection

热休克蛋白对抗原虫感染的作用

基本信息

批准号：
08044296
负责人：
HIMENO Kunisuke
金额：
$ 4.74万
依托单位：
University of Tokushima
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08044296/
关键词：
Toxoplasma gondii Protection to protozoa infection Heat shock proteins gamma delta T cells Resistance to infection 細胞性寄生性 HSP マクロファージ γδT細胞 NKT細胞病原性アポトーシス

项目摘要

Exposing cells to a variety of stressful conditions such us elevated temperature, chemical intoxication or infection leads to the transcription of a set of genes and subsequently, to the synthesis of a family of polypeptides called heat shock proteins (HSPs). These proteins have retained highly conserved amino acid sequences throughout evolution from prokaryotes to eukaryotes. Since HSPs are proposed as common immunogens involved in infections with unmerous microorganisms, these proteins are being studied in detail. However, it is difficult to define the role of HSPs in infection and immunity, since these are HSPs in the both hosts and microorganisms in infection states, and since they are highly homologous. For intracellular parasites, HSPs may be essential for the adaptation of those organisms to the strict environment of hosts, and for transformation of organisms to infectious form. HSPs of parasites also function as immunodominant peptides that can be recognized by host humoral and … More cellulaar immune systems. On the other hand, HSPs synthesized as they respond to stress during certain infection may actually play a role in host defense. Thus, HSPs expressed either the hosts or parasites may have a potential to modulate the host-parasite relationship.We investigated the involvement of the 65 kDa heat shock protein (HSP65) in infection with an obligate intracellular protozoan Toxoplasma gondii (T.gondii). In humans, this ubiquitous parasite rarely causes diseases in individuals of normal immunocompetence, but it produces severe symptoms as an opportunistic infection in immunocompromized hosts, for example patient with AIDS.Considering the increasing number of hosts with AIDS throughout the world, it is important to understand the life cycle of this protozoan and how the protective immunity achieves towards this and other parasites.We present here that HSP65 expression on/in host macrophages is induced by gammadelta T cells and that it plays an important role in resistance against infection with T.gondii. Further , we found that HSP65 can be effective in protecting infected macrophages from apoptotic cell death. Analysis of these relationships should contribute to host-parasite interactions with T.gondii and should guide speculation on role playd by HSPs in infection with numerous intracellular pathogens other than T.gondii such as Leishmania major, Trypanosoma cruzi and malaria protozoa. Less

将细胞暴露于各种应激条件下，例如高温、化学中毒或感染，会导致一组基因的转录，随后合成一系列称为热休克蛋白（HSP）的多肽，这些蛋白质被高度保留。从原核生物到真核生物的整个进化过程中，HSP 被认为是参与无数微生物感染的常见免疫原，因此正在对这些蛋白质进行详细研究，但是，很难确定其作用。感染和免疫中的热休克蛋白，因为它们在感染状态下的宿主和微生物中都有热休克蛋白，并且由于它们具有高度同源性，因此对于细胞内寄生虫来说，热休克蛋白可能对于这些生物体适应宿主的严格环境至关重要。寄生虫的热休克蛋白也起到免疫显性肽的作用，可以被宿主体液和细胞免疫系统识别。另一方面，热休克蛋白在某些情况下对应激做出反应时会合成。感染实际上可能在宿主防御中发挥作用，因此，宿主或寄生虫表达的 HSP 可能具有调节宿主-寄生虫关系的潜力。我们研究了 65 kDa 热休克蛋白 (HSP65) 在专性感染中的作用。细胞内原生动物弓形虫 (T.gondii) 在人类中，这种普遍存在的寄生虫很少在免疫功能正常的个体中引起疾病，但作为机会性病原体，它会产生严重的症状。免疫功能低下宿主的感染，例如艾滋病患者。考虑到全世界艾滋病宿主数量不断增加，了解这种原生动物的生命周期以及保护性免疫如何实现这种寄生虫和其他寄生虫非常重要。我们在此提出宿主巨噬细胞上/内的 HSP65 表达是由 γδ T 细胞诱导的，并且它在抵抗弓形虫感染方面发挥着重要作用。此外，我们发现 HSP65 可以有效保护感染。对这些关系的分析应有助于宿主-寄生虫与弓形虫的相互作用，并应指导热休克蛋白在弓形虫以外的许多细胞内病原体（如大型利什曼原虫、克氏锥虫和疟疾）感染中所起的作用的推测。原生动物较少。