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

PONCE N.E.; SANMARCO L.M.; EBERHARDT N.; GARCIA M.C.; RIVAROLA W.; CANO R.C.; AOKI M.P.

JOURNAL OF IMMUNOLOGY

AMER ASSOC IMMUNOLOGISTS

Lugar: Bethesda; Año: 2016 vol. 197 p. 814 - 814

0022-1767

ncreasing evidence demonstrates that generation of extracellular adenosine from ATP, which is hydrolyzed by the CD39/CD73 enzymepair, attenuates the inflammatory response and deactivates macrophage antimicrobial mechanisms. Although CD73 is emerging asa critical pathway and therapeutic target in cardiovascular disorders, the involvement of this ectonucleotidase during myocardialinfection has not been explored. Using a murine model of infection with Trypanosoma cruzi, the causal agent of Chagas cardiomyopathy,we observed a sudden switch from the classical M1 macrophage (microbicidal) phenotype toward an alternative M2 (repairing/antiinflammatory) phenotype that occurred within the myocardium very shortly after BALB/c mice infection. The observed shift in M1/M2rate correlated with the cardiac cytokine milieu. Considering that parasite persistence within myocardium is a necessary and sufficientcondition for the development of the chronic myocarditis, we hypothesized that CD73 activity ma