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

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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