DURING ACUTE PHASE OF Trypanosoma cruzi INFECTION DISTURBED MITOPHAGY CONTRIBUTES TO DAMAGED MITOCHONDRIA ACCUMULATION IN EFFECTOR CD4 T CELLS LEADING TO APOPTOSIS

ANA, Y; BAIGORRÍ, RE; CERBAN, FM; STEMPIN, CC

Congreso; Reunión de Sociedades de Biociencias 2021 - LXIX REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA; 2021

Chagas disease is characterized by inefficient host immune response during acute phase of infection, enabling the establishment of chronic disease. We have recently demonstrated that acute infection triggers mitochondrial ROS (mROS) production and mitochondrial alterations in effector CD4 T cells leading to functional alterations and apoptosis. The aim of our work was to evaluate the mechanism involved in the accumulation of damaged mitochondria, and if this could be prevented by the antioxidant N-acetyl cysteine (NAC) or the mitophagy inducer Nicotinamide Riboside (NR). To achieve this, CD4 T cells were isolated from spleen of non-infected (NI), acute (AP) and chronic phase (CP) infected BALB/c mice, with 500 trypomastigotes. Mitophagy was evaluated using mitochondrial potential independent probe (MTgreen) and antibodies for LC3 and LAMP1.Cells were cultured with or without chloroquine and colocalization was evaluated by confocal microscopy. CD4 T cells from AP cultured with chloroquine did not show significant increase in MTgreen and LAMP1 colocalization compared to CCCP-treated NI CD4 T cells used as positive control (*p<0,05) suggesting a defect in mitophagy. Then, we aimed to evaluate by flow cytometry, mROS production, frequency of cells with damaged mitochondria and apoptosis in effectorCD4 T cells from AP infected mice treated with NAC, NR and vehicle as control. We did not found differences between NAC and control group. In contrast, NR treatment reduced the percentage ofCD4 T cells with damaged mitochondria (*p<0.05), although we did not observed difference in mROS production. Moreover, apoptosis frequency was also diminished (**p<0.01). Depolarized mitochondria accumulation, probably due to a defect in mitophagy, could be restored by NR, and thus prevent apoptosis. Taken together, this evidence stablishes association between accumulated damaged mitochondria, and impaired mitophagy leading to apoptosis in CD4 T cells during acute T. cruzi infection.