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

ANA, YAMILE; BAIGORRÍ, RUTH ELIANA; STEMPIN, CINTHIA C.; ROJAS MARQUEZ, JORGE D.; CERBAN, FABIO M.; PIACENZA, LUCÍA; RADI, RAFAEL

Congreso; LXVIII Reunión Anual de la Sociedad Argentina de Inmunología; 2020

SAI

Chagas disease is characterized by inefficient host immune response during acute phase enabling the establishment of chronic disease. Imbalances in T cells´s metabolism can be detrimental. The aim of our work was to evaluate metabolic and mitochondrial parameters in CD4 T cells during T. cruzi infection. To achieve this, CD4 T cells were isolated from spleen of non-infected (NI), acute (AP) and chronic (CP) infected BALB/c mice, with 500 trypomastigotes. Mitochondrial parameters were measured by FACS combining potential-dependent and independent probes while mitochondrial ROS (mROS) was measured using MitoSOX. Seahorse XF24 was employed for bioenergetics analysis. We found a raised basal glycolysis and high oxidative metabolism in CD4 T cells from the AP. Besides, these cells showed increased proton leak and uncoupling protein 3 (UCP3) expression that correlates with our previous results that demonstrated mROS accumulation, mitochondrial membrane potential depolarization, PD1 expression and less IL-2 released (analyzed by ELISA) after stimulation during AP of infection. Furthermore, CD4 T cells with mitochondrial alterations (MA) displayed an activated phenotype, and were more prone to apoptosis. This phenotype was dependent on TCR signalling, since MA in CD4 T cells from AP were significantly reduced in OTII mice. Mn-Superoxide Dismutase 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-acetyl cysteine (NAC). It is probably that antioxidant availability may not be sufficient to avoid MA rendering these cells more susceptible to apoptosis. Thus, our results showed that acute infection triggers an exacerbated metabolism together with mROS production in CD4 T cells. Taken together, this evidence stablishes association between disturbed metabolism and impaired CD4 T cell response during acute T. cruzi infection.