Myocardium-derived cytokine drives monocyte recruitment and macrophage profile in Trypanosoma cruzi-infected heart tissue

SANMARCO L.M.; PONCE N.E.; AOKI M.P.

Mar del Plata

Congreso; LXII Reunión Científica de la Sociedad Argentina Inmunología; 2014

Sociedad Argentina de Inmunología

The ability of monocytes to mobilize and traffic to where they are needed is central for their functions in promoting immune defense and in driving inflammation (pro-inflammatory/anti-microbial macrophages M1) or tissue regeneration (fibrosis/wound healing M2). The factors that determine cardiac macrophage influx to cardiac tissue and their profile during infection are not well characterized. The aim of the present work is was to study the kinetic of different macrophage subsets and the crosstalk between monocyte influx and cardiomyocytes-released cytokines (cq). Previously we found that M1 and M2 macrophages present differential kinetic in myocardium of infected Balb/c mice. Here, We observed a significant decrease in granulocytes and M2 infiltrate on heart tissue of infected IL6 deficient (IL6KO) vs wild type C57BL/6 (WT) mice (p<0.001, p<0.01 respectively). Adoptive transference of WT and IL6KO spleen cells into infected IL6KO or WT mice showed that only WT cells infiltrate myocardium of IL6KO mice while both transfected Populations transferred populations goet into WT myocardium at the same level. Considering That WT and IL6KO cells are were proportionally equal in peripheral blood in both transfected transferred mice groups of mice, the IL6 released by myocardium is was determinant for macrophage influx. While early at infection (4dpi), WT exhibited higher levels of M1 (F4/80+CD86+CD206-) than M2 (F4/80+CD86-CD206+) (p<0.05), later the macrophages are were biased to M2 throughout the infection. In contrast, IL6KO never showed M2 macrophage profile. In accord, they had more myocardial damage (%CK-MB) (p<0.01) that correlated with increased heart levels of proinflammatory cq IL17 and TNFa, and lower levels IL4 and of anti-inflammatory cq such as IL4 and IL10 (p<0.05). As a result, infected IL6KO havepresented decreased survival rate (p<0.001). Together our data demonstrated a homeostatic role for IL6 released by cardiomyocytes as a critical factor of for macrophages influx and M2 polarization, this may set the basis for an adequate immune defense and anti-inflammatory response.