Role of HSP65 in host protection against intracellular protozoan infection.

HSP65 在宿主免受细胞内原生动物感染的保护中的作用。

基本信息

批准号：
06454200
负责人：
HIMENO Kunisuke
金额：
$ 4.48万
依托单位：
Tokushima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06454200/
关键词：
Heat shock protein Protozoan infection Toxoplasma Leishmania Virulence gammadelta T cell Protective immunity 原虫感染防御 αβT細胞エスケープ機構

项目摘要

We previously reported that induction of host 65 kDa heat shock protein (HSP65) closely correlates with protection against Toxoplasma gondii (T.gondii) infection, and T cells, especially gammadelta T cells, play an important role in protection and HSP65 expression.T.gondii infection induces HSP65 expression in peritoneal macrophages and depletion of gammadelta T cells resulted in marked attenuation of its espression. This T cell subset secretes IFN-gamma and TNF-alpha as determined by using RT-PCR method. These cytokines are known to activate macrophages. Neutralization of these cytokines with corresponding antibodies prior to infection suppresses HSP65 expression, indicating that HSP65 expression attributed by gammadelta T cells is dependent on these cytokines. We speculate that HSP65 participates in protection by means of preservation of macrophages, in coincident with its native role as "molecular chaperon". Peritoneal macrophages and macrophage cell line, J774 cells infected in vitro with T.gondii undergo apoptosis. Expression of HSP65 on these cells, being induced with above cytokines, prevents them from apoptosis. However, this effect is reversed by the addition of antisense oligonucleotide for this protein. These results indicate that HSP65 prevent apoptosis of macrophages, which contributes to protection.A similar relationship between protective immunity and HSP65 expression was also seen in mice infected with Leishmania major and Trypanosoma cruzi.

我们之前报道过，宿主65 kDa热休克蛋白（HSP65）的诱导与对弓形虫（T.gondii）感染的保护密切相关，而T细胞，特别是γδ T细胞，在保护和HSP65表达中发挥着重要作用。弓形虫感染诱导腹腔巨噬细胞中 HSP65 的表达，并且 γδ T 细胞的耗竭导致其表达显着减弱。通过 RT-PCR 方法测定，该 T 细胞亚群分泌 IFN-γ 和 TNF-α。已知这些细胞因子可激活巨噬细胞。在感染前用相应的抗体中和这些细胞因子会抑制HSP65的表达，表明γδT细胞引起的HSP65表达依赖于这些细胞因子。我们推测 HSP65 通过保存巨噬细胞来参与保护，这与其作为“分子伴侣”的天然作用一致。体外感染弓形虫的腹膜巨噬细胞和巨噬细胞系 J774 细胞发生凋亡。这些细胞上 HSP65 的表达被上述细胞因子诱导，可防止细胞凋亡。然而，通过添加该蛋白质的反义寡核苷酸可以逆转这种效应。这些结果表明HSP65可防止巨噬细胞凋亡，从而起到保护作用。在感染重大利什曼原虫和克氏锥虫的小鼠中也观察到保护性免疫和HSP65表达之间的类似关系。