Limited induction of Foxp3+ regulatory T cell during experimental Trypanosoma cruzi infection allows the generation of robust effector responses and parasite control

C ARAUJO FURLAN; J TOSELLO BOARI; C RODRIGUEZ; F CANALE; F FIOCCA VERNENGO; C BECCARIA; A GRUPPI; C MONTES; E ACOSTA RODRIGUEZ

Lucca (Barga)

Congreso; Gordon Research Conference: Immunochemistry & Immunobiology; 2016

Gordon Research Conference

CD4+CD25+Foxp3+ regulatory T cells (Tregs) present a dual role during infections as they limit immunopathology but also restrain immunity to the pathogen. Regulatory responses during T. cruzi infection have been poorly characterized and Tregs role remains controversial. We previously determined that after 11 days of infection, Tregs frequency is significantly reduced in the periphery of infected mice, in part due to impaired induction of peripheral Tregs.Here, our aim was to better characterize Tregs phenotype and function and their biological relevance during T. cruzi infection. For this, Foxp3-GFP mice were infected with 5000 T. cruzi parasites (Tulahuén) and Tregs were characterized by flow cytometry. Upon infection, Tregs upregulated CD44, CTLA-4, GITR, PD1, CD39, CXCR3 and CD103 expression, consistent with activated phenotype. Furthermore, at day 20 post-infection a large proportion of Tregs produced LAP and IL-10. However, in vitro suppression assays using Tregs purified from non-infected or 20-day-infected mice revealed that Tregs suppressive capacity is not increased by activation mediated by T. cruzi. To assess the role of reduced Tregs frequency in T. cruzi infection, we performed adoptive transfer experiments of in vitro induced Tregs. Intravenous injection of Tregs at day 11 post-infection resulted in a significant decrease in the frequency and numbers of total and parasite-specific CD8+ T cells in the spleen and liver at day 17 post-infection. Accordingly, these mice showed increased parasitemia. We conclude that the limitation in the numbers of activated Tregs during T. cruzi infection may be critical to allow the development of the effector response and parasite control, but might also foster immunopathology.