THE INNATE IMMUNE RESPONSE TO TRYPANOSOMA CRUZI EXPERIMENTAL INFECTION IS INVOLVED IN CARDIOMYOCYTE PROTECTION FROM APOPTOSIS: IN VIVO AND IN VITRO EVIDENCES

PONCE N.E.; ; CANO R.C.; CARRERA - SILVA A.; GEA S.; AOKI M.P

La Plata - Buenos Aires

Congreso; XVIII Meeting ISHR Latin American Section; 2010

International Society for Heart Research

Cardiac innate immunity plays a main role in defense response and heart`s homeostasis. We have reported that T. cruzi, the ethiological agent of chagasic cardiomyopathy, protects isolated cardiomyocytes from apoptosis. Our aim was to elucidate cardiomyocyte innate immune response to T. cruzi infection and its possible cytoprotection role. We found that the parasite strongly increased TLR2 expression, but not TLR4, in BALB/c neonatal cardiomyocyte cultures (CC). Among the several cytokines tested, we detected a rapid, sustained and NF-kB-dependent production of IL6. Transfection of CC with a dominant-negative TLR2 plasmid blocked the T. cruzi-induced survival effect 48h after serum starvation as well as it diminished the IL6 production elicited by the infection (P<0.001). Cultures treated with IL6 neutralizing antibody abolished the parasite-induced cytoprotection (P<0.02). In addition, we found that infected cardiomyocytes-produced IL6 increased p-STAT3 in CC. In vitro results agreed with the in vivo increased expression of TLR2 and BCL-2 in cardiac fibers during the acute infection. Our results suggest that the triggering of TLR2 signalling, followed by IL6 production and STAT3 activation, plays a key role in T. cruzi-elicited cardiomyocyte survival.