Trypanosoma cruzi infection and cruzipain modulate the mRNA level for Toll-like receptor 2 activating multiple signaling pathways in cardiomyocytes

AOKI, MARIA DEL PILAR; CARRERA SILVA, ANTONIO; CANO, ROXANA; PELLEGRINI, ANDREA; TANOS, TAMARA; COSO, OMAR; GEA, SUSANA

Ciudad de Córdoba

Congreso; VII Congreso Latinoamericano de Inmunología; 2005

Asociación Latinoamericana de Inmunología

Trypanosoma cruzi infection and cruzipain modulate the mRNA level for Toll-like receptor 2 activating multiple signaling pathways in cardiomyocytes Aoki, MP1; Carrera, A1; Cano, R1; Pellegrini, A1; Tanos, T2; Coso, O2;Gea, S1. 1CIBICI-CONICET. FCQ. UNC.  paoki@bioclin.fcq.unc.edu.ar 2 LFyBM-CONICET. FCEyN. UBA. Argentina Toll-like receptors (TLRs) are a family of signal transducing molecules which are critical for the induction of innate immunity. They have been associated with cardiomyocyte survival and parasite control. Previously, we demonstrated that cardiomyocytes subjected to serum starvation and infected with T. cruzi or treated with cruzipain (Cz) displayed an increase in cell viability. Here we investigated the modulation of TLR2 expression and cell signaling pathways activated by T. cruzi infection and Cz treatment of cardiomyocytes. Neonatal BALB/c mouse myocytes were cultured with Cz (10ug/ml) or infected with T. cruzi (Tulahuen strain). Employing Annexin V binding, we observed that inhibition of PI3K (Ly294002) and MEK1 (PD098059) but not JNK (SP600125) or p38 MAPK (SB203580) abrogated the antiapoptotic effect of Cz (P<0.01). In accord, phosphorylation of Akt and ERK1/2 were observed after Cz treatment or T. cruzi infection. Furthermore, cleavage of caspase-3 after serum starvation was considerably diminished by Cz. Bcl-2, p-Bad and Bcl-xL expression as well as TLR2-mRNA were significantly increased by Cz and differentially modulated by PI3K and MEK1 inhibitors. In addition, TLR2 messenger was down-regulated at 1h but up-regulated at 24h post-infection. We conclude that T. cruzi infection and Cz treatment of cardiomyocytes activate PI3K/Akt and MEK1/ERK1/2 signaling pathways and are able to modulate TLR2 expression.