Toll-like Receptor-2 and Interleukine-6 Mediate Cardiomyocyte Protection from Apoptosis during Trypanosoma cruzi Murine Infection.

PONCE NE, CANO RC, CARRERA-SILVA EA, LIMA AP, GEA S, AOKI MP

MEDICAL MICROBIOLOGY AND IMMUNOLOGY

SPRINGER

Lugar: Berlin; Año: 2012 p. 145 - 155

0300-8584

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 cellswere 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 antiapoptotic 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 antiapoptotic 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.