CD73 Inhibition Shifts Cardiac Macrophage Polarization toward a Microbicidal Phenotype and Ameliorates the Outcome of Experimental Chagas Cardiomyopathy

PONCE, NE; SANMARCO, LM; EBERHARDT, N; GARCÍA, MC; RIVAROLA G; CANO, RC; AOKI, MP

JOURNAL OF IMMUNOLOGY

AMER ASSOC IMMUNOLOGISTS

Lugar: Bethesda; Año: 2016

0022-1767

!--[if gte mso 9]> Increasingevidence demonstrate that generation of extracellular adenosine from ATP, whichis hydrolyzed by the CD39/CD73 enzyme pair, attenuates the inflammatoryresponse and deactivates macrophage anti-microbial mechanisms. Although CD73 isemerging as a critical pathway and therapeutic target in cardiovasculardisorders, the involvement of this ectonucleotidase during myocardial infectionhas not been explored. Using a murine model of infection with Trypanosomacruzi, the causal agent of Chagas cardiomyopathy, we observed a sudden switchfrom classical M1 macrophage (microbicidal) phenotype toward alternative M2(repairing/anti-inflammatory) phenotype that occurred within the myocardiumvery shortly after BALB/c mice infection. The observed shift in M1/M2 ratecorrelated with the cardiac cytokine milieu. Considering that parasitepersisten