Role of Heat Shock Protein against Protozoan Infection

热休克蛋白对抗原虫感染的作用

• 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

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

将细胞暴露在各种压力条件下，如高温、化学中毒或感染，会导致一组基因的转录，随后会合成一种称为热休克蛋白（HSPs）的多肽家族。这些蛋白在原核生物到真核生物的进化过程中保留了高度保守的氨基酸序列。由于热休克蛋白被认为是参与无数微生物感染的常见免疫原，这些蛋白质正在被详细研究。然而，很难确定热休克蛋白在感染和免疫中的作用，因为这些热休克蛋白在感染状态的宿主和微生物中都是热休克蛋白，而且它们是高度同源的。对于细胞内寄生虫，热休克蛋白可能是这些生物体适应宿主的严格环境和将生物体转化为感染性形式所必需的。寄生虫的热休克蛋白还具有免疫优势肽的功能，可以被宿主的体液免疫系统和细胞免疫系统识别。另一方面，热休克蛋白是在某些感染过程中对应激反应合成的，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热休克蛋白可能具有调节宿主-寄生虫关系的潜力。我们研究了65 kDa热休克蛋白（HSP65）在专性细胞内原生动物刚地弓形虫（弓形虫）感染中的作用。在人类中，这种普遍存在的寄生虫很少在免疫能力正常的个体中引起疾病，但它在免疫功能低下的宿主中作为机会性感染产生严重症状，例如艾滋病患者。考虑到世界上越来越多的艾滋病宿主，了解这种原生动物的生命周期以及对这种寄生虫和其他寄生虫的保护性免疫如何实现是很重要的。我们在这里提出HSP65在宿主巨噬细胞上/内的表达是由γ δ T细胞诱导的，并且它在抵抗弓形虫感染中起重要作用。此外，我们发现HSP65可以有效地保护感染的巨噬细胞免于凋亡细胞死亡。对这些关系的分析将有助于了解宿主-寄生虫与弓形虫的相互作用，并有助于推测热休克蛋白在除弓形虫以外的许多细胞内病原体（如利什曼原虫、克氏锥虫和疟疾原虫）感染中所起的作用。少

项目成果

Sakai,T.: "Expression of adhesion molecules on LEC rat peripheral CD4^+ T cells:Unique expression of LEA-1 and LECAM-1." J.Trace Elem.Exp.Med.10. 81-88 (1997)

Sakai,T.：“LEC 大鼠外周 CD4+ T 细胞上粘附分子的表达：LEA-1 和 LECAM-1 的独特表达。”

Hisaeda,H.: "Heat shock protein 65 induced by γδ T cells prevents apoptosis of macrophages and contributes to host defense in mice infected with Toxoplasma gondii." J.Immunology. 159. 2375-2381 (1997)

Hisaeda, H.：“γδ T 细胞诱导的热休克蛋白 65 可以防止巨噬细胞凋亡，并有助于感染弓形虫的小鼠的宿主防御。J.Immunology。”

Hisaeda,H.: "The role of host-derived heat-shock protein in immunity against Toxoplasma gondii infection." Parasitology Today. 13. 465-468 (1997)

Hisaeda,H.：“宿主源性热休克蛋白在弓形虫感染免疫中的作用。”

Himeno,K.: "Medical Aspects of Proteases and Protease Inhibitors." Katunuma,N., Fritz,H., Kido,H., and Travis,J., 9 (1997)

Himeno,K.：“蛋白酶和蛋白酶抑制剂的医学方面。”

Himeno,K.: "Contribution of 65-kDa heat shock protein induced by gamma and delta T cells to protection against Toxoplasma gondii infection." Immunol.Res.15. 258-264 (1996)

Himeno,K.：“γ 和 δ T 细胞诱导的 65 kDa 热休克蛋白对预防弓形虫感染的贡献。”