Purinergic signaling differentially modulates tissue immune response fate in experimental Chagas disease.

THEUMER, MARTÍN G.; EBERHARDT, NATALIA; AOKI, MARIA P.; GARCÍA, M.; SANMARCO, LILIANA M.; PONCE, NICOLÁS E.

Foz de Iguazú

Congreso; Purines 2018 International; 2018

Background and Objective: Chagas cardiomyopathy, caused by the intracellular parasite Trypanosoma cruzi, constitutes a major public health problem in Latin America due to its prevalence and mortality. Despite the development of life-long immunity, the immune system fails to completely clear the parasites that persist within host tissues. One potential immunosuppressive system that could regulate anti-parasitic immune functions is CD73 ectoenzyme/adenosine (ADO) pathway. We previously reported that transient pharmacological inhibition of CD73 during the early acute phase of murine T. cruzi infection induced microbicidal mechanisms, a reduction in cardiac parasite load and the consequent improvement in chronic cardiomyopathy outcome (Ponce et al. J Immunol, 2016, 197:3). The aim of this study was to characterize the effect of the genetic abrogation of CD73 on the microbicidal immune response in different T. cruzi-target tissues. Methods and Results: To this aim, immune system modulation and its implications in T. cruzi infection response were comparatively studied in heart, liver and visceral adipose tissue (VAT) from CD73 knockout (KO) and C57BL/6 (WT) infected mice (Tulahuen strain trypomastigotes). The kinetics of cardiac macrophage (Ma) subsets showed a predominant inflammatory/M1 (CD86+ CD206-) (p