A multifactorial mechanism in the superior antimalarial activity of alpha-C-GalCer.

A multifactorial mechanism in the superior antimalarial activity of alpha-C-GalCer.
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DOI:
10.1155/2010/283612
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发表时间:
2010
影响因子:
--
通讯作者:
Tsuji M
Tsuji M
中科院分区:
其他
文献类型:
--
作者:
Schmieg J;Yang G;Franck RW;Tsuji M

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我们之前已经证明,α-半乳糖神经酰胺(α-GalCer)的c -糖苷类似物α-C-GalCer对啮齿动物疟原虫约利疟原虫的肝脏阶段表现出比其亲本糖脂α-GalCer更好的抑制活性。在这项研究中,我们证明NK细胞和IL-12是α-C-GalCer表现出优越活性的关键因素。令人惊讶的是,α-C-GalCer减少Th2细胞因子(包括IL-4)的产生,对其相对于α-GalCer的优越治疗活性没有影响。最后,我们发现α-C-GalCer在体内可诱导树突状细胞(dc)的成熟时间延长,并增强小鼠不变的Vα14 (Vα14i) NKT细胞的增殖反应,这两者也可能在一定程度上有助于α-C-GalCer在体内的优越活性。
We have previously shown that the C-glycoside analog of α-galactosylceramide (α-GalCer), α-C-GalCer, displays a superior inhibitory activity against the liver stages of the rodent malaria parasite Plasmodium yoelii than its parental glycolipid, α-GalCer. In this study, we demonstrate that NK cells, as well as IL-12, are a key contributor for the superior activity displayed by α-C-GalCer. Surprisingly, the diminished production of Th2 cytokines, including IL-4, by α-C-GalCer has no affect on its superior therapeutic activity relative to α-GalCer. Finally, we show that the in vivo administration of α-C-GalCer induces prolonged maturation of dendritic cells (DCs), as well as an enhanced proliferative response of mouse invariant Vα14 (Vα14i) NKT cells, both of which may also contribute to some degree to the superior activity of α-C-GalCer in vivo.
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