Trypanosoma cruzi: Phosphatidylinositol 3-kinase and protein kinase B activation is associated with parasite invasion

Multiple signal transduction events are triggered in the host cell during i nvasion by the protozoan parasite Trypanosoma cruzi. Here, we report the re gulation of host cell phosphatydilinositol 3-kinase (PI3K) and protein kina se B (PKB/Akt) activities by T. cruzi during parasite-host cell interaction . Treatment of nonphagocytic cells (Vero, L6E9, and NIH 3T3) and phagocytic cells (human and J774 murine macrophages) with the selective PI3K inhibito rs Wortmannin and LY294002 significantly impaired parasite invasion in a do se-dependent fashion. A strong activation of PI3K and PKB/Akt activities in Vero cells was detected when these cells were incubated with trypomastigot es or their isolated membranes. Consistently, we were unable to detect acti vation of PI3K or PKB/Akt activities in host cells during epimastigote (non infective) membrane-host cell interaction. Infection of transiently transfe cted cells containing an inactive mutant PKB showed a significant inhibitio n of invasion compared with the active mutant-transfected cells, T. cruzi P I3K-like activity was also required in host cell invasion since treatment o f trypomastigotes with PI3K inhibitors prior to infection reduced parasite entry. Taken together, these results indicate that PI3K and PKB/Akt activat ion in parasites, as in host cells induced by T. cruzi, is an early invasio n signal required for successful trypomastigote internalization. (C) 2001 A cademic Press.