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

• Published in: Microbiology and immunology Vol. 52; no. 11; p. 539
• Main Authors: Murata, Eri, Hashimoto, Muneaki, Aoki, Takashi
• Format: Journal Article
• Language: English
• Published: Australia 01.11.2008
• Subjects: Animals; Apoptosis; CASP8 and FADD-Like Apoptosis Regulating Protein - metabolism; Chagas Disease - parasitology; Cysteine Proteinase Inhibitors - pharmacology; HeLa Cells; Humans; Immunoprecipitation; Leupeptins - pharmacology; Proteasome Inhibitors; Repressor Proteins - metabolism; Trypanosoma cruzi - parasitology; Ubiquitin-Protein Ligases - metabolism; Ubiquitination
• ISSN: 0385-5600; 1348-0421
• DOI: 10.1111/j.1348-0421.2008.00073.x

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 cFLIP(L), a mammalian inhibitor of death receptor signaling. Here it is shown that ubiquitination of cFLIP(L,) 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 cFLIP(L), 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.