Interaction between cFLIPL and Itch, a ubiquitin ligase, is obstructed in Trypanosoma cruzi-infected human cells

Abstract

Death receptor-mediated host cell apoptosis, a defense strategy for elimination by the immune system of parasite-infected cells, is inhibited by Trypanosoma cruzi, the causative agent of Chagas' disease. It has previously been reported by us that, in infected cells, T. cruzi upregulates and exploits cFLIPL, a mammalian inhibitor of death receptor signaling.Here it is shown that ubiquitination of cFLIPL, leading to proteasomal degradation, is inhibited in parasite-infected cells. The extent of expression of Itch, a protein thought to be an ubiquitin ligase for cFLIPL, was found to be equivalent in T. cruzi-infected and in uninfected cells.However, co-immunoprecipitation analysis showed that the interaction between cFLIP L and Itch is strongly inhibited in T. cruzi-infected cells. This unique parasite strategy, which has not been reported in any other pathogen-infected cells, may allow the host cell to accumulate cFLIP L, eventually resulting in the inhibition of apoptosis of T. cruzi-infected cells. © 2008 The Societies and Blackwell Publishing Asia Pty Ltd.