EXACERBATED METABOLISM AND MITOCHONDRIAL REACTIVE OXYGEN SPECIES CONTRIBUTE TO MITOCHONDRIAL ALTERATIONS AND APOPTOSIS IN CD4 T CELLS DURING ACUTE PHASE OF TRYPANOSOMA CRUZI INFECTION

PIACENZA, MARÍA LAURA; BAIGORRI, RUTH ELIANA; ANA, YAMILE; FOZZATTI, LAURA; STEMPIN, CINTHIA CAROLINA; MÁRQUEZ, JORGE DAVID ROJAS; CERBAN, FABIO MARCELO

Congreso; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2020; 2020

Chagas disease is characterized by inefficient host immuneresponse during acute phase enabling the establishmentof chronic disease. Imbalances in T cells´s metabolismcan be detrimental. The aim of our work wasto evaluate metabolic and mitochondrial parameters inCD4 T cells during T. cruzi infection. To achieve this, CD4T cells were isolated from spleen of non-infected (NI),acute (AP) and chronic (CP) infected BALB/c mice, with500 trypomastigotes. Mitochondrial parameters weremeasured by FACS combining potential-dependent andindependent probes while mitochondrial ROS (mROS)was measured using MitoSOX. Seahorse XF24 wasemployed for bioenergetics analysis. We found a raisedbasal glycolysis and high oxidative metabolism in CD4 Tcells from the AP. Besides, these cells showed increasedproton leak and uncoupling protein 3 (UCP3) expressionthat correlates with our previous results that demonstratedmROS accumulation, mitochondrial membranepotential depolarization, PD1 expression and less IL-2released (analyzed by ELISA) after stimulation during APof infection. Furthermore, CD4 T cells with mitochondrialalterations (MA) displayed an activated phenotype, andwere more prone to apoptosis. This phenotype was dependenton TCR signalling, since MA in CD4 T cells fromAP were significantly reduced in OTII mice. Mn-SuperoxideDismutase expression, involved in mROS detoxification,was increase during the AP and CP of infection.Apoptosis observed in CD4 T cells with depolarized mitochondria,was prevented by incubation with N-acetylcysteine (NAC). It is probably that antioxidant availabilitymay not be sufficient to avoid MA rendering these cellsmore susceptible to apoptosis. Thus, our results showedthat acute infection triggers an exacerbated metabolismtogether with mROS production in CD4 T cells. Takentogether, this evidence stablishes association betweendisturbed metabolism and impaired CD4 T cell responseduring acute T. cruzi infection.