Adenosine-derived from CD73 enzymatic activity modulates the activation status of cardiac macrophages during experimental Trypanosoma cruzi infection

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

Buenos Aires

Congreso; LASID 2015; 2015

The myocarditis caused by Trypanosoma cruzi infection still remains as the major global infectious heart disease. Among the leukocyte arriving to the infected heart, infiltrating macrophages play a key role in the anti-parasite response and tissue repair mechanisms by adapting their phenotype and functions to environmental cues. We hypothesize that cardiac macrophage polarization in Chagas disease is strongly influenced by adenosine. Extracellular ATP is converted into adenosine by two ecto-enzymes (CD39 and CD73) and both metabolites modulate differentially the immune response. Our previous results demonstrated that the manipulation of purinergic system in infected mice modulates the infiltrating macrophage phenotype, the cytokine profile and the cardiomyopathy outcome in chronic Chagas disease. Our aim was to study the cardiac immune response against T. cruzi infection in CD73-deficient mice. Thekinetic of infiltrating macrophage subsets showed that Proinflammatory/microbicidal phenotype (M1) predominated over anti-Inflammatory/tissue-repairing profile (M2) at evaluated days post-infection (dpi) (p<0.001). In contrast, in C57BL/6 (WT) mice, the M1 subset diminished and M2 significantly increased and remained sustained since the 7dpi. The elevated parasitemia found in CD73KO compared to WT mice (at 14 and 21dpi, p<0.01) correlated with the diminished serum levels of nitric oxide in deficient mice (p<0.05 at 14dpi). Moreover, myocardialspecific injury biomarker (Creatine Kinase-MB:total CK rate) was significantly augmented at 4 and 14 dpi (vs C57BL/6 p<0.01). In conclusion, CD73 modulates the early shift of cardiac macrophagepolarization and participates in the control of parasite replication. This study provides a new gateway to manipulate the cardiac macrophage profile.