Abstract: |
We have previously shown that the C-glycoside analog of alpha-galactosylceramide (alpha-GalCer), alpha-C-GalCer, displays a superior inhibitory activity against the liver stages of the rodent malaria parasite Plasmodium yoelii than its parental glycolipid, alpha-GalCer. In this study, we demonstrate that NK cells, as well as IL-12, are a key contributor for the superior activity displayed by alpha-C-GalCer. Surprisingly, the diminished production of Th2 cytokines, including IL-4, by alpha-C-GalCer has no affect on its superior therapeutic activity relative to alpha-GalCer. Finally, we show that the in vivo administration of alpha-C-GalCer induces prolonged maturation of dendritic cells (DCs), as well as an enhanced proliferative response of mouse invariant V alpha 14 (V alpha 14i) NKT cells, both of which may also contribute to some degree to the superior activity of alpha-C-GalCer in vivo. |