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: 10044297
• 负责人: HIMENO Kunisuke
• 金额: $ 4.1万
• 依托单位: Tokushima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10044297/
• 关键词: Protozoa infection; Heat shock proteins; Malaria; HSP 90; Resistace to infection

Among HSP families, HSP90 has been given much attention. This protein is involved in cellular functions by forming complexes with many cellular proteins such as kinases, phosphatases, nuclear hormone receptors, actin, tubulin, and the proteasome. Fruit flies with homozygous mutations of HSP90 gene cannot survive and those with heterozygous mutation frequently show morphological abnormalities. Over-expression of HSP90 enhances the virulence of the yeast Saccharomyces cerevisiae in mice. We have studied the expression mechanism of parasite. HSP90 and its correlation with virulence of murine malaria parasite. HSP90 was strongly expressed in parasite from B6 mice infected with the L strain of P. yoelii and only slightly expressed in parasite from mice infected with the L strain. Interestingly, HSP90 expression was not detected in parasites from SCID mice treated with anti-CD4 and anti-TcR-αβ or anti-IFN-γmonoclonal antibodies, but not in parasite from those treated with anti-CD8, anti-TcR- … More γδ or anti-IL-4 antibody. By using SCID mice transferred with CD4ィイD1-ィエD1 or CD8ィイD1-ィエD1 splenic cells of BALB/c, we demonstrated again that CD4ィイD1+ィエD1 T cells but not CD8ィイD1+ィエD1 T cells were indispensable for the expression of parasite HSP90. Immunoelectron microscopic analysis confirmed that massive HSP90 signal was expressed in nuclei of schizonts and merozoits but only slightly in cytoplasma of these parasites and in trophozoits and gametocytes. Reactive oxygen species (ROS) and nitric oxide (NO) but not IFN-γ treatment increased HSP90 expression in parasite cultured in vitro. HSP90 expression was decreased significantly at later period of infection with the L strain, possibly because of immune-suppression during the infection. Parasite from immune-component mice was highly infective than that from SCID mice, suggesting that parasites expressing HSP90 have higher infectivity than parasites not expressing HSP90. Finally, the amino acid sequence of P. yoelii HSP90 was deduced from the cDNA sequence. In conclusion, parasite HSP90 is a virulent factor and induced by host immune response.In brief, our results show that HSPs appear to play crucial roles in host-parasite interaction. Less

在HSP家族中，HSP 90受到了广泛的关注。这种蛋白质通过与许多细胞蛋白质如激酶、磷酸酶、核激素受体、肌动蛋白、微管蛋白和蛋白酶体形成复合物而参与细胞功能。HSP 90基因纯合突变的果蝇不能存活，杂合突变的果蝇常表现出形态异常。过表达HSP 90增强酿酒酵母对小鼠的毒力我们研究了寄生虫的表达机制。热休克蛋白90与鼠疟原虫毒力的关系HSP 90在感染约氏疟原虫L株的B6小鼠体内呈强阳性表达，而在感染约氏疟原虫L株的小鼠体内呈弱阳性表达。有趣的是，在用抗CD 4和抗TcR-αβ或抗IFN-γ单克隆抗体处理的SCID小鼠的寄生虫中未检测到HSP 90表达，但在用抗CD 8、抗TcR-αβ或抗IFN-γ单克隆抗体处理的SCID小鼠的寄生虫中未检测到HSP 90表达。 ...更多信息 γδ或抗IL-4抗体。用BALB/c小鼠脾细胞CD 4 + D1-CD 8 + D1-免疫电镜分析证实，大量的HSP 90信号表达在寄生虫和裂殖子的细胞核中，但在这些寄生虫的细胞质中以及滋养体和配子体中只有轻微的表达。活性氧（ROS）和一氧化氮（NO）处理能增加体外培养的疟原虫HSP 90的表达，而IFN-γ处理不能。L株感染后期HSP 90表达明显下降，可能与感染过程中的免疫抑制有关。来自免疫组小鼠的寄生虫比来自SCID小鼠的寄生虫具有更高的感染性，表明表达HSP 90的寄生虫比不表达HSP 90的寄生虫具有更高的感染性。最后，从cDNA序列推导出约氏疟原虫HSP 90的氨基酸序列。综上所述，寄生虫HSP 90是一种毒力因子，是由宿主免疫反应诱导的，在宿主-寄生虫相互作用中起着重要作用。少

项目成果

Sakai, T., Hisaeda, H., Ishikawa, H., Maekawa, Y., Zhang, M., Nakano, Y., Takeuchi, T., Matsumoto, K., Good, R.A., and Himeno, K.: "Expression and role off heat shock protein 65 in macrophages during Trypanosoma cruzi infection : involvement of HSP65 in p

Sakai, T.、Hisaeda, H.、Ishikawa, H.、Maekawa, Y.、Zhang, M.、Nakano, Y.、Takeuchi, T.、Matsumoto, K.、Good, R.A. 和 Himeno, K.：

Zhang,M.: "Macrophages expressing heat-shock protein 65 play an essential role in protection of mice infected with Plasmodium yoelii."Immunology. 97. 611-615 (1999)

张，M.：“表达热休克蛋白 65 的巨噬细胞在保护感染约氏疟原虫的小鼠中发挥着重要作用。”免疫学。

Zhang, M., Hisada, H., Kano, S., Matsumoto, Y., Hao, Y., Looaresuwan, S., Aikawa, M., and Himeno, K.: "Antibody responses to heat shock protein in patients with severe malaria in Thailand."Parasitology International. (in press).

张，M.，久田，H.，卡诺，S.，松本，Y.，郝，Y.，Looaresuwan，S.，相川，M.，和姬野，K.：“患者对热休克蛋白的抗体反应

Zhang, M., Hisada, H., Tsuboi, T., Torii, M., Sakai, T., Nakano, Y., Ishikawa, H., Maekawa, Y., Good, R.A., and Himeno, K.: "Stage-specific expression of heat shock protein 90 in murine malaria parasite Plasmodium yoelii."Exp. Parasitol.. 93. 61-65 (1999)

张 M.、久田 H.、坪井 T.、鸟居 M.、酒井 T.、中野 Y.、石川 H.、前川 Y.、古德 R.A. 和姬野 K.：

Sakai,Tohru: "DNA immunization with Plasmodium falciparum serine repeat antigen:Regulation of humoral immune response by coinoculation of cytokine expression plasmid." Parasitology International,in press.(1999)

Sakai，Tohru：“用恶性疟原虫丝氨酸重复抗原进行 DNA 免疫：通过细胞因子表达质粒的共接种调节体液免疫反应。”