EARLY TREG CELL DEPLETION DURING TRYPANOSOMA CRUZI INFECTION PROMOTES CD8+ T CELL IMMUNITY AND PARASITE CONTROL IN THE ACUTE AND CHRONIC PHASES

ARAUJO FURLÁN CL; BOCCARDO S; RODRIGUEZ C; MONTES CL; GRUPPI A; ACOSTA RODRIGUEZ EV

Congreso; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2020; 2020

We reported that after Trypanosoma cruzi (Tc) infection, Tregs undergo a marked and sustained reduction in frequency. This naturalcontraction of the Treg response was critical to allow the emergenceof protective anti-parasite CD8+ T cell immunity in the acute phase.Accordingly, we previously demonstrated that Treg depletion at day(d) 5 post-infection (pi) but not at d11pi impacted on the magnitudeof anti-parasite CD8+ T cell response and the ability to control parasite replication in the acute phase. Considering this, we hypothesized that Tregs may exert a role during early events of T cell priming. To test this, DEREG mice were infected with Tc and injected withdiphtheria toxin (DT) or PBS at d5 and 6pi. The next day, DT-treatedanimals showed increased numbers of B cells, monocytes and neutrophils in the spleen compared to controls (p<0.05). Furthermore,CD86 expression was upregulated on splenic dendritic cells andmacrophages of DT-injected mice in contrast to controls (p<0.05).Evaluation of the expression of different suppression markers onTregs from infected mice did not evidence significant phenotypicactivation of splenic Tregs at 5 dpi. This suggests that an undetermined mediator and/or the basal expression of multiple regulatorymarkers might be involved in the suppression. Finally, we lookedif Treg depletion at early time points had an effect over the effectorresponse and parasite control at the chronic phase. We found thatmice treated with DT as above showed higher frequency of total andactivated CD8+ T cells infiltrating liver, skeletal muscle and heartat d97pi than control mice, which coincided with reduced parasiteburden in spleen and liver (p<0.05). Altogether, our results suggestthat during Tc infection Tregs suppress the CD8+ T cell response atthe priming stage through indirect mechanisms. These events at theacute phase would have late effects over the effector, likely pathogenic, response and parasite control at the chronic phase.