The ability of monocytes/macrophages (Mo/Ma) to mobilize to where they are needed is central for their functions in promoting immune defense and driving inflammation (pro-inflammatory/anti-microbial M1 Ma) or tissue regeneration (fibrosis/wound healing M2 Ma). The factors that determine Mo/Ma recruitment into cardiac tissue and their profile during T. cruzi infection have not been characterized. The aim of the present work was to study the kinetic of cardiac Ma subsets and the crosstalk between Mo/Ma and infected myocardium. We observed a significant decrease in infiltrating granulocytes and Ma in heart tissue of infected IL6 deficient (KO) mice vs C57BL/6 (WT) mice (p<0.001, p<0.01 respectively). Adoptive transference of WT and KO spleen cells into infected KO or WT mice showed that only WT cells infiltrated the myocardium of KO mice while both transferred populations got into WT myocardium at comparable levels. Considering that WT and KO cells were proportionally equal in peripheral blood of both transferred groups of mice, the IL6 released by myocardium was clue for Mo/Ma influx. Additionally, while early at infection (4dpi) WT mice exhibited higher levels of cardiac M1 Ma (F4/80+CD86+CD206-) than M2 Ma (F4/80+CD86-CD206+) (p<0.05), later the Ma populations were biased to sustained M2 subset. In contrast, KO mice never displayed a dominant M2 profile, and underwent more myocardial damage (measured as %CK-MB) (p<0.01) that correlated with increased heart levels of inflammatory cytokines (IL17 and TNFa) and lower levels of anti-inflammatory mediators (IL4 and IL10) (p<0.05). In consequence, infected KO presented increased mortality (p<0.001).Together our data demonstrate a homeostatic role for IL6 released by myocardium as a critical factor for Mo/Ma influx and M2 polarization, these mechanisms may contribute to the development of an adequate immune defense and a concomitant anti-inflammatory response.
