Toll-like receptor-2 and interleukin-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 vol. 201 p. 145 - 155

0300-8584

Local innate immunity plays a key role in initiating and coordinating homeostaticand defense responses in the heart. We have previously reported that thecardiotropic parasite Trypanosoma cruzi, the etiological agent of Chagas disease,protects cardiomyocytes against growth factor deprivation-induced apoptosis. Inthis study, we investigated cardiomyocyte innate immune response to T. cruziinfection and its role in cellular protection from apoptosis. We found thatToll-like receptor (TLR) 2-expressing cells were strongly increased by theparasite in BALB/c neonatal mouse cardiomyocyte cultures. Using adominant-negative system, we showed that TLR2 mediated cardiomyocyte survival and the secretion of interleukin (IL) 6, which acted as an essential anti-apoptoticfactor. Moreover, IL6 released by infected cells, as well as the recombinantbioactive cytokine, induced the phosphorylation of the signal transducers andactivators of transcription-3 (STAT3) in cultured cardiomyocytes. In accord with the in vitro results, during the acute phase of the infection, TLR2 expressionincreased 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 innateresponse of cardiomyocytes and the pro-survival effect evoked by the parasite.