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

EBERHARDT, N; PONCE, NE; SANMARCO, LM; AOKI, MP

Jornada; LXIII Reunión Anual de la Sociedad Argentina de Inmunología; 2015

The myocarditis caused by Trypanosoma cruzi infection still remains as the major globalinfectious heart disease. Among the leukocyte arriving to the infected heart,infiltrating macrophages macrophage play a key role in the anti-parasite responseand tissue repair mechanisms by adapting their phenotype and functions toenvironmental cues. We hypothesize that cardiac macrophage polarization inChagas disease is strongly influenced by adenosine. Extracellular ATP is convertedinto adenosine by two ecto-enzymes (CD39 and CD73) and both metabolites modulatedifferentially the immune response. Our previous results demonstrated that themanipulation of purinergic system in infected mice modulates the infiltrating macrophagephenotype, the cytokine profile and the cardiomyopathy outcome in chronicChagas disease. Our aim was to study the cardiac immune response against T.cruzi infection in CD73-deficientmice. The kinetic of infiltrating macrophage subsets showed thatpro-inflammatory/microbicidal phenotype (M1) predominated overanti-inflammatory/tissue-repairing profile (M2) at evaluated dayspost-infection (dpi) (p<0.001). Incontrast, in C57BL/6 (WT) mice, the M1 subset diminished and M2 significantly increasedand remained sustained since the 7dpi. The elevated parasitemia found in CD73KOcompared 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, myocardial-specific 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 shiftof cardiac macrophage polarization and participates in the control of parasite replication. This studyprovides a new gateway to manipulate the cardiac macrophage profile