EXACERBATED METABOLISM, MITOCHONDRIAL ROS PRODUCTION AND MITOCHONDRIAL DEPOLARIZATION IN CD4 T CELLS DURING ACUTE PHASE OF TRYPANOSOMA CRUZI INFECTION

FOZZATTI, LAURA; PIACENZA LUCIA; STEMPIN, CINTHIA; ANA, YAMILE; CERBAN, FABIO

Tucumán

Congreso; LVII Reunión Anual de la Sociedad Argentina de Inmunología; 2019

Sociedad Argentina de Inmunología

Chagas disease is characterized by inefficient host immune response during acute phase (AP) enabling the establishment of chronic disease. Imbalances in T cell´s metabolism can be detrimental. We have previously shown that CD4 T cells displayed increase mitochondrial ROS (mROS) production and mitochondrial alterations (MA) during AP of Trypanosoma cruzi infection. The aim of this work was to determine whether these parameters were related to PD-1 expression, to evaluate antioxidant mechanisms and metabolic status of CD4 T cells during infection. CD4 T cells were isolated from spleen of BALB/c mice, non infected (controls) and infected with 500 trypomastigotes. MA were measured by FACS combining potential-dependent and independent probes while mROS was measured using MitoSOX. We observed that acute infected animals have higher frequency of CD4 T cells with MA that produce mROS with high PD-1 expression, compared to control and chronic animals. MA were confirmed by electron microscopy. Antioxidant proteins were evaluated by qPCR, western blot and immunofluorescence. The transcription factor FOXO3a involved in ROS detoxification, and Mn-Superoxide Dismutase, one of the main antioxidant mechanisms, were increased during acute and chronic infection compared to control mice. Moreover, we studied metabolic profile by Seahorse extracellular flux analyzer. CD4 T cells from AP of infection are highly oxidative, with increased proton leak, ATP production, in combination with an activated glycolytic program, compared to control animals. Our result showed that infection triggers an exacerbated metabolism together with mROS production. Antioxidant mechanism may be not enough to avoid MA during AP of infection