Purinergic signaling participates in phenotypic modulation of cardiac macrophages during experimental Trypanosoma cruzi infection.

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

Mar del Plata

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Inmunología; 2016

SAI

Extracellular ATP and adenosine are increasingly recognized as key mediators of theimmune response to several pathogens. ATP can act as a danger signal initiating aninnate immune response, while adenosine generally serves as a regulatory feedbackmechanism to limit inflammation. Macrophages (Ma) are highly plastic cells and dependingon the micro-environmental stimulation they exhibit a proinflammatory (classical/M1) or ananti-inflammatory (reparatory/M2) phenotype. Considering that ATP is converted toADP/AMP and then to adenosine by CD39 and CD73 enzymes, respectively, we havereported that transient pharmacological inhibition of CD73 ectoenzyme during the earlyacute phase of murine T. cruzi infection induces microbicidal mechanisms, reduction incardiac parasite load and improves the outcome of chronic cardiomyopathy. The aim ofthis study was to characterize the role of purinergic system in regulatory mechanismstriggered in cardiac tissue during T. cruzi infection. The kinetic of cardiac Ma subsetsshowed that M1 predominated over M2 profile throughout the infection in CD73KO mice(p<0.001). In contrast, C57BL/6 (WT) mice presented diminished M1 subset andsignificantly increased M2, which remained sustained since 7 dpi. Strikingly, CD73KOmice had higher parasitemia than WT mice (14 and 21dpi, p<0.05) and this correlated withdiminished nitric oxide (NO) serum levels in deficient mice (21 dpi, p<0.001). Notably,CD73KO mice had diminished cardiac parasite load compared to WT (21 and 28 dpi,p<0.05) but augmented liver parasite load (21 dpi, p<0.05). The decrease in cardiacparasitism correlated with the M1 Ma phenotype prevalence and augmented tissue NO levels (21 dpi, p<0.05) compared to WT mice. In conclusion, ectonucleotidase pathwayparticipates in cardiac adaptation of Ma subsets in order to interrupt macrophage-mediatedinflammation. This study provides new insight on the role of purinergic signaling in thephenotypic modulation of immune cells.