A Multifactorial Mechanism in the Superior Antimalarial Activity ofα-C-GalCer

[摘要] We have previously shown that the C-glycoside analog ofα-galactosylceramide (α-GalCer),α-C-GalCer, displays a superior inhibitory activity against the liver stages of the rodent malaria parasitePlasmodium yoeliithan 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 byα-C-GalCer. Surprisingly, the diminished production of Th2 cytokines, including IL-4, byα-C-GalCer has no affect on its superior therapeutic activity relative toα-GalCer. Finally, we show that the in vivo administration ofα-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 ofα-C-GalCer in vivo.

[学科分类] 基础医学