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Molecular immunological aspects on protective mechanism for Babesia spp infection in mice

小鼠巴贝虫感染保护机制的分子免疫学研究

基本信息

批准号：
06454129
负责人：
ONO Kenichiro
金额：
$ 4.54万
依托单位：
University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1996
项目状态：
已结题

项目摘要

Comparative studies on the characteristics of protozoan glucose metabolism and protective mechanism for infection in two Babesia species, Babesia microti (BM) and Babes rodhaini (BR), were crried out from 1994 to 1997.To elucidate characteristics of glucose metabolism in these two species, various enzyme activities related to glucose metabolism and mitochondrial functions were examined. The lactate dehydrogenase activity of BM was significantly smaller than that of BR,whereas TCA cycle enzymes activity of BM were larger than those of BR.Therefore, it is suggested that BM and BR depend on aerobic and anaerobic pathways, respectively. On the results of mitochoudrial functions, the activities of electron transport, ubiquinone function, ATP synthesis, and proton pump were found in both BM and BR.However, BM showed smaller effects of various inhibitors used on mitochondrial functions compared with BR.These results suggested that the relative importance of mitochondria in the energy metaboli … More sm, at least in tems of an electron transport activity, is larger in BM than in BR.To elucidate protective mechanism aginst BM and BR infection, the role of T cell subpopulation were investigated in Lyt-2* T cell and L3T4* T cell depleted mice. Depletion of Lyt-2* cells enhanced the resistance to BM infection, whercas it increased the susceptibility to BR infection. In contrast, depletion of L3T4* cells increased susceptibility to BM infection, while it enhanced resistance to BR infection. It was suggested that the roles of Lyt-2* and L3T4* T cells in the protective cell-mediated immune response at the initial phase of infection were different between BM-and BR-infected mice. Expression of gamma-IFN mRNA and interleukin-4 (IL-4) mRNA in splenic L3T4* T cell from BM-and BR-infected mice were examined. The subset of splenic L3T4* T cell developing at the initial phasc of infection was helper T cell type-1 cell (Th 1), which enhanced cell-mediated immune response in BM,and helper T cell type-2, which induced humoral one in BR.In order to adress the mechanism for diffcrentia activation of Th cell subsets, the expression of IL-12 and IL-10 mRNA were examined. In BM-ifected mice the onsct of IL-12 mRNA expression was carlier than that in BR-infected mice, while the onset of IL-10 mRNA in BM-infected was later than that in BM.Therfore, it was suggested that the order of priming of cither IL-12 or IL-10 in the carly stage regulated the differenciation of Th cells into Th 1 in BM infection or Th 2 in BR infection. Less

1994 ~ 1997年对两种巴贝斯虫（Babesmicroti（BM）和Babesrodhaini（BR））的葡萄糖代谢特性和感染保护机制进行了比较研究。BM的乳酸脱氢酶活性显著小于BR，而TCA循环酶活性则大于BR，因此，BM和BR分别依赖于好氧和厌氧途径。线粒体功能测定结果表明，BM和BR均具有电子传递、泛醌功能、ATP合成和质子泵等功能，但BM的各种抑制剂对线粒体功能的影响均小于BR。这些结果表明，BM在能量代谢中的相对重要性与BR的线粒体功能有关。 ...更多信息为阐明抗BM和BR感染的保护机制，在Lyt-2 ~* T细胞和L_3T_4 ~* T细胞缺失的小鼠中研究了T细胞亚群的作用。Lyt-2* 细胞的耗竭增强了对BM感染的抵抗力，同时增加了对BR感染的易感性。相反，L3 T4 * 细胞的耗竭增加了对BM感染的易感性，同时增强了对BR感染的抗性。这表明，在BM和BR感染的小鼠中，Lyt-2* 和L3 T4 * T细胞在感染初期的保护性细胞介导的免疫应答中的作用是不同的。检测了BM和BR感染小鼠脾脏L3 T4 * T细胞γ-IFN mRNA和IL-4 mRNA的表达。在感染初期，脾L_3T_4 ~* T细胞亚群为辅助性T细胞1型（Th 1），在BM中可增强细胞免疫应答，在BR中则为辅助性T细胞2型，可诱导体液免疫应答。BM感染小鼠IL-12 mRNA的表达开始较BR感染小鼠早，而IL-10 mRNA的表达开始较BM晚。因此，早期IL-12或IL-10的启动顺序调节Th细胞向BM感染的Th 1或BR感染的Th 2分化。少