Molecular and metabolic mechanism involved in the impairment of CD4 T cell response during Trypanosoma cruzi infection

ROJAS M, JD; STEMPIN CC; ANA, Y; BRUGO, MB; FOZZATTI, L; CERBAN, FM

Mar del Plata

Congreso; LXVI Reunión Sociedad Argentina de Inmunología.; 2018

We have shown previously that CD4 T cells shows increased mitochondrial ROS (ROSm) production and mitochondrial alterations during the acute phase of Trypanosoma cruzi infection. In addition, we have observed decreased glucose uptake in these cells. In order to determine the energy balance in CD4 T cells during T. cruzi infection we evaluate AMPK phosphorylation (p-AMPK) in these cells purified from spleen of Balb/c mice infected with 500 trypomastigotes (tp) of Tulahuen strain at different times post infection (p.i) compared to CD4 T cells purified from control mice. We observed that CD4 T cells from the acute phase of infection showed an increase of p-AMPK indicating unfavorable metabolic conditions in these cells. On the other hand, it has been demonstrated that CD11a and CD49d can be used as strategy to evaluate ?specific? CD4 T cells. We observed an increase in the frequency of this population in CD4 T cells from T. cruzi infected mice. Moreover, we detected an increase in the frequency of ?specific? CD4 T cells with mitochondrial alterations during the acute phase of infection, measured by combining a potential-dependent (MitoOrange) and a potencial-independent mitochondrial dye (MitoGreen) by FACS. To address if these alterations are related to the load of the parasite, BALB/c mice were infected i.p. with 500, 1000 and 5000 (tp) and CD4 T cells were purified from spleen of uninfected (control) or infected mice at different days p.i. We observed an increase in ROSm production and mitochondrial alterations and reduced glucose uptake in CD4 T cells from infected mice compared to control cells. However, there were not differences in these parameters between the different groups of animals infected with different parasite load. However, apoptosis evaluated by FACS in these groups of animals was increased compared to control cells and was slightly bigger in BALB/C mice infected with 5000 tp. Moreover, we have observed that apoptosis was also increased in ROSm+ CD4 T cells during the chronic phase of infection. These results may indicate that T. cruzi induces mitochondrial alteration leading to metabolic dysregulation in CD4 T cells during acute phase of infection that have an impact in the outcome of these cells during the chronic phase of infection.