DIFFERENTIAL LOCALIZATION OF CD73 IN TARGET TISSUES OF TRYPANOSOMA CRUZI INFECTION AND THE EFFECT OF THIS ADENOSINE GENERATING ECTOENZYME ON LOCAL PARASITE REPLICATION

BERGERO GASTÓN; EBERHARDT NATALIA; MAZZOCO YANINA; THEUMER MARTÍN GUSTAVO; AOKI PILAR

Tucumán

Congreso; LXVII Reunión Científica Anual de la Sociedad Argentina de Inmunología; 2019

Sociedad Argentina de Inmunología

Growing evidence demonstrates a critical role of purinergic system in the modulation of theimmune response and tissue repair. Damaged cells release the pro-inflammatory moleculeATP, which is metabolized by the ectonucleotidases CD39 and CD73 to the antiinflammatory mediator adenosine (ADO). Thus, the balance between ATP/ADO is knownto determine the outcome of inflammation/infection. Here, we explored the cellular sourceof CD73 ectoenzyme expression in different Trypanosoma cruzi infected tissues and theimpact of its activity in local parasite replication. Through confocal analysis ofimmunofluorescence assays we found that immune cells exhibited significantly higherlevels of CD73 expression than parenchymal cells at 7 days post-infection (dpi), whilecardiomyocytes, adipocytes and hepatocytes expressed lower amount of this ectoenzyme(p<0.001 immune cells vs parenchymal cells). Deficiency of CD73 activity (CD73KO) led toa diminished cardiac parasite burden, measured by real-time PCR, compared to its wildtype (WT) counterpart (p<0.001 at 21dpi and p<0.05 at 28dpi). Unexpectedly, parasitemiawas substantially raised in CD73KO mice in comparison with WT mice (p<0.05 at 14dpiand 21dpi), suggesting the existence of tissue reservoir/s outside myocardium. Indeed,CD73KO liver and visceral adipose tissue (VAT) showed increased parasite burden (liver:p<0.001 at 21dpi and VAT: p<0.01 at 21 and 28dpi) associated with a reduced ATP/ADOratio (p<0.05 heart vs liver and VAT) and the lack of substantial microbicidal immuneresponse. These data reveal that the purinergic system has a tissue-dependent impact onparasite replication and persistence