Early Treg cell depletion during Trypanosoma cruzi infection promotes CD8+ T cell immunity and parasite control in the acute and chronic phases

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

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 natural contraction of the Treg response was critical to allow the emergence of 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 magnitude of 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 with diphtheria toxin (DT) or PBS at d5 and 6pi. The next day, DT-treated animals 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 and macrophages of DT-injected mice in contrast to controls (p<0.05). Evaluation of the expression of different suppression markers on Tregs from infected mice did not evidence significant phenotypic activation of splenic Tregs at 5 dpi. This suggests that an undetermined mediator and/or the basal expression of multiple regulatory markers might be involved in the suppression. Finally, we looked if Treg depletion at early time points had an effect over the effector response and parasite control at the chronic phase. We found that mice treated with DT as above showed higher frequency of total and activated CD8+ T cells infiltrating liver, skeletal muscle and heart at d97pi than control mice, which coincided with reduced parasite burden in spleen and liver (p<0.05). Altogether, our results suggest that during Tc infection Tregs suppress the CD8+ T cell response at the priming stage through indirect mechanisms. These events at the acute phase would have late effects over the effector, likely pathogenic, response and parasite control at the chronic phase.