Deficiency of CD73 activity promotes protective cardiac immunity against Trypanosoma cruzi infection but permissive environment in visceral adipose tissue

EBERHARDT, NATALIA; THEUMER, MARTÍN GUSTAVO; CANO, ROXANA CAROLINA; SANMARCO, LILIANA MARIA; GARCÍA, MÓNICA CRISTINA; AOKI, MARIA PILAR; SANMARCO, LILIANA MARIA; GARCÍA, MÓNICA CRISTINA; AOKI, MARIA PILAR; BERGERO, GASTÓN; PONCE, NICOLAS ERIC; BERGERO, GASTÓN; PONCE, NICOLAS ERIC; EBERHARDT, NATALIA; THEUMER, MARTÍN GUSTAVO; CANO, ROXANA CAROLINA

BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR BASIS OF DISEASE

ELSEVIER SCIENCE BV

Año: 2020 vol. 1866

0925-4439

Damaged cells release the pro-inflammatory signal ATP, which is degraded by the ectonucleotidases CD39 and CD73 to the anti-inflammatory mediator adenosine (ADO). The balance between ATP/ADO is known to determine the outcome of inflammation/infection. However, modulation of the local immune response in different tissues due to changes in the balance of purinergic metabolites has yet to be investigated. Here, we explored the contribution of CD73-derived ADO on the acute immune response against Trypanosoma cruzi parasite, which invades and proliferates within different target tissues. Deficiency of CD73 activity led to an enhanced cardiac microbicidal immune response with an augmented frequency of macrophages with inflammatory phenotype and increased CD8+ T cell effector functions. The increment of local inducible nitric oxide (NO) synthase (iNOS)+ macrophages and the consequent rise of myocardial NO production in association with reduced ADO levels induced protection against T. cruzi infection as observed by the diminished cardiac parasite burden compared to their wild-type (WT) counterpart. Unexpectedly, parasitemia was substantially raised in CD73KO mice in comparison with WT mice, suggesting the existence of tissue reservoir/s outside myocardium. Indeed, CD73KO liver and visceral adipose tissue (VAT) showed increased parasite burden associated with a reduced ATP/ADO ratio and the lack of substantial microbicidal immune response. These data reveal that the purinergic system has a tissue-dependent impact on the host immune response against T. cruzi infection.