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：
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

项目摘要

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，通过与许多Cellaru蛋白UCH形成复合物作为激酶，phosshatase，Nucrear荷尔蒙受体，肌动蛋白，微管蛋白和蛋白酶体，这引起了很多关注。无法生存，而杂合突变则表现出酵母菌的形态异常。 l菌株。 BALB/C的脾细胞，我们再次证明了CD4 D1+Yi D1+Yier D1 T细胞在寄生虫HSP90的表达中是BLE的。在体外培养的HSP90表达中，HSP90表达在L菌株的后期显着降低，因为在感染过程中，HSP90的表达显着降低cDNA序列总结，寄生虫HSP90是一个病毒性因素，并由宿主免疫反应诱导。在简短的情况下，我们的结果表明，HSP似乎在宿主 - 寄生虫相互作用中起着至关重要的作用。