title: Toll-like receptor-2 and interleukin-6 mediate cardiomyocyte protection from apoptosis during Trypanosoma cruzi murine infection.
abstract: Local innate immunity plays a key role in initiating and coordinating homeostatic and defense responses in the heart. We have previously reported that the cardiotropic parasite Trypanosoma cruzi, the etiological agent of Chagas disease, protects cardiomyocytes against growth factor deprivation-induced apoptosis. In this study, we investigated cardiomyocyte innate immune response to T. cruzi infection and its role in cellular protection from apoptosis. We found that Toll-like receptor (TLR) 2-expressing cells were strongly increased by the parasite in BALB/c neonatal mouse cardiomyocyte cultures. Using a dominant-negative system, we showed that TLR2 mediated cardiomyocyte survival and the secretion of interleukin (IL) 6, which acted as an essential anti-apoptotic factor. Moreover, IL6 released by infected cells, as well as the recombinant bioactive cytokine, induced the phosphorylation of the signal transducers and activators of transcription-3 (STAT3) in cultured cardiomyocytes. In accord with the in vitro results, during the acute phase of the infection, TLR2 expression increased 2.9-fold and the anti-apoptotic factor Bcl-2 increased 4.5-fold in the cardiac tissue. We have clearly shown a cross-talk between the intrinsic innate response of cardiomyocytes and the pro-survival effect evoked by the parasite.
authors: Centro de Investigaciones en Bioquímica Clínica e Inmunología CIBICI-CONICET, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende s/n, 5000, Córdoba, Argentina.
authors: Nicolás Eric
authors: NE
authors: Ponce
authors: Roxana Carolina
authors: RC
authors: Cano
authors: Eugenio Antonio
authors: EA
authors: Carrera-Silva
authors: Ana Paula
authors: AP
authors: Lima
authors: Susana
authors: S
authors: Gea
authors: Maria Pilar
authors: MP
authors: Aoki
mesh_terms: D000818:Animals; D017209:Apoptosis; D014355:Chagas Disease / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D015850:Interleukin-6 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology* / Q000472:pathogenicity*
chemical_list: D015850:Interleukin-6; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2