INVESTIGADORES
AOKI Maria Del Pilar
congresos y reuniones científicas
Título:
The signaling pathway PI3K/Akt is involved in IL-6 production, TLR2 expression and survival of cardiomyocytes during Trypanosoma cruzi infection
Autor/es:
MP AOKI; CARRERA SILVA A; PELLEGRINI A.; GUIÑAZÚ NL; CANO RC; GEA S
Lugar:
Rio de Janeiro
Reunión:
Congreso; 13º Congreso Internacional de Inmunología (ICI).; 2007
Institución organizadora:
Sociedad Científica
Resumen:
Pathogen
recognition receptors from the TLR family are crucial for the
generation of effective immunity but are also involved in mammalian cell
survival. Little is known about the innate immunity of cardiomyocytes
and parasite infection. We previously demonstrated that T. cruzi
infection as well as cruzipain, a major parasite antigen, protected
isolated cardiac cells against apoptosis induced by growth factor
deprivation. The anti-apoptotic effect was mediated by PI3K/Akt and
MEK1/ERK signaling pathways. Here we analyzed the interplay between the
cardiomyocyte innate immune response and T. cruzi infection. Neonatal
BALB/c mouse myocytes were cultured with cruzipain or infected with
different doses of trypomastigotes from Tulahuen strain. We found that
parasite infection as well as cruzipain strongly up-regulate the
membrane expression and mRNA of TLR2 but not TLR4 evaluated by flow
cytometry, immunocytochemistry and RT-PCR respectively. Employing ELISA
assays, we observed that both stimuli strongly increase the release of
the pro-inflammatory cytokine IL-6 (medium 950.8±120.2pg/ml; cruzipain
4748.3±920.2pg/ml; trypomastigotes 3107.9±980.2pg/ml) but not IL-4
anti-inflammatory cytokine. In addition, NF-kB transcription factor
translocates to the cardiac cell nucleus after T. cruzi infection
indicating that it is activated by the parasite. The pharmacological
inhibition of NF-kB with TPCK (25 µM) or PI3K with Ly294002 (25 µM) lead
to a complete abrogation of cruzipain induced anti-apoptosis, IL-6
release and TLR2 up-regulation. These results strongly suggest the
existence of a very tight link among cardiomyocyte innate immunity and
its response to T. cruzi infection.