Congresos y reuniones científicas
Título:
MITOCHONDRIAL DYSFUNCTION MAY INFLUENCE CD4 T CELL METABOLISM DURING THE ACUTE PHASE OF TRYPANOSOMA CRUZI INFECTION.
Autor/es:
ANA, YAMILE; JORGE ROJAS M; LAURA FOZZATTI; CERBAN F; CINTHIA STEMPIN
Reunión:
Congreso; REUNIÓN DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA; 2017
Resumen:
We have shown that decreased function of CD4 T cell during acute phase of Trypanosoma cruzi infection is related to increase of PD-1 and gene related to anergy in lymphocytes (GRAIL) expression, reduced IL-2 production and lower mTOR activation. Moreover, it has been demonstrated that upon activation T cells undergo metabolic reprogramming to glycolysis and mitochondrial biogenesis required to support their functions. Since mTOR is a central regulator of metabolism, we investigate the status of metabolic pathways in CD4 T cells during T. cruzi infection. BALB/c mice were infected i.p. with 500 trypomastigotes of Tulahuen strain and CD4 T cells were purified from spleen of uninfected (control) or infected mice at different days post infection (p.i.). We evaluated expression of nutrient transporters CD71 (transferrin), CD98 (aminoacids) and Glut1 (glucose) as well as uptake of a fluorescent glucose analog 2NBDG by FACS. We did not observed differences in CD71, CD98 and Glut1 expression in ex vivo CD4 T cells from infected animals compared with controls. After aCD3/aCD28 stimulation, CD4 T cells from control and 42 day p.i animals were able to upregulate these transporters besides increased the uptake of 2-NBDG. However, CD4 T cells from 21 day p.i. animals showed no differences compared to unstimulated cells. To study mitochondrial dysfunction we combined a potential-dependent (MitoOrange) and a potencial-independent mitochondrial dye (MitoGreen) to identify CD4 T cells with depolarized mitochondria as well as measured mitochondrial ROS (mROS) production (MitoSox) by FACS. At day 15 p.i. a significantly higher fraction of CD4 T cells had depolarized mitochondria and produced increased levels of mROS compared with control or 42 day p.i. animals, being mROS production greater in CD4 T cells with high PD-1 expression. These results may indicate that T. cruzi induces mitochondrial alteration leading to metabolic dysregulation of CD4 T cells during acute phase of infection.