AOKI MARIA DEL PILAR
Congresos y reuniones científicas
Título:
Purinergic signaling participates in phenotypic modulation of cardiac macrophages during experimental Trypanosoma cruzi infection
Autor/es:
EBERHARDT, N; PONCE, NE; SANMARCO, LM; AOKI, MP
Reunión:
Congreso; annual meeting of the Argentinean Immunology Society; 2016
Resumen:
Extracellular ATP and adenosine are increasinglyrecognized as key mediators of the immune response to several pathogens. ATPcan act as a danger signal initiating an innate immune response, whileadenosine generally serves as a regulatory feedback mechanism to limit inflammation.Macrophages (Ma) are highly plastic cells and depending on themicro-environmental stimulation they exhibit a proinflammatory (classical/M1)or an anti-inflammatory (reparatory/M2) phenotype. Considering that ATP isconverted to ADP/AMP and then to adenosine by CD39 and CD73 enzymes,respectively, we have reported that transient pharmacological inhibition ofCD73 ectoenzyme during the early acute phase of murine T. cruzi infection induces microbicidal mechanisms, reduction incardiac parasite load and improves the outcome of chronic cardiomyopathy. Theaim of this study was to characterize the role of purinergic system inregulatory mechanisms triggered in cardiac tissue during T. cruzi infection. The kinetic of cardiac Ma subsets showed thatM1 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,CD73KO mice had higher parasitemia than WT mice (14 and 21 dpi, p<0.05) andthis correlated with diminished nitric oxide (NO) serum levels in deficientmice (21 dpi, p<0.001). Notably, CD73KO mice had diminished cardiac parasiteload compared to WT (21 and 28 dpi, p<0.05) but augmented liver parasiteload (21 dpi, p<0.05). The decrease in cardiac parasitism correlated withthe 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 purinergicsignaling in the phenotypic modulation of immune cells.
