Study of the role of tissue resident regulatory T cells during Trypanosoma cruzi infection

SANTIAGO BOCCARDO; CINTIA L. ARAUJO FURLAN; CONSTANZA RODRIGUEZ; CAROLINA P ABRATE; LAURA ALMADA; ADRIANA GRUPPI; CAROLINA L. MONTES; EVA V. ACOSTA RODRIGUEZ

Mar del plata

Congreso; Reunion Conjunta SAIC SAI SAFIS 2018; 2018

Sociedad Argentina de Inmunología

Tissue resident CD4+Foxp3+ regulatory T cells (tisTregs) have emerged as a specialized Treg subset that exhibit phenotypic, functional and transcriptional profiles particular to each tissue. tisTregs not only regulate immune effector function as lymphoid Tregs but also modulate several non-immune biological processes and maintain tissue homeostasis. T. cruzi triggers a strong effector response that controls parasite spreading and may promote tissue damage and immune pathology. Our previous results showed that during Tc infection, there is an impaired induction of Tregs, and particularly of those with markers related to ?tissue protection?, such as ST2, KLRG-1 and IL-18R in Blood, Spleen, Liver and Skeletal Muscle (SM).Our current aim is to evaluate the levels of cytokines involved in tisTregs development during Chagas Disease. To this end, Foxp3-GFP C57BL/6 mice were infected with 5000 T. cruzi parasites (Tulahuen) and level of IL-33 and IL-18 were determined in plasma, and Spleen and SM lysates by ELISA. We found IL-33 levels decreased and IL-18 levels increased after 14 and 21 dpi in plasma and spleen, but they both increased after 21dpi in SM (p<0.05). We also sought to evaluate the effector response during Tc infection and whether it correlates with Tregs development in Chagas Disease. With the same infection protocol, we evaluated by flow cytometry the frequency of Tregs and TSKB20 specific CD8 T cells in Blood, Spleen, Liver and SM. We found an inverse correlation between both populations in all tissues assesed. Our preliminary results suggest that tisTregs may not be induced during T. cruzi infection and this may be associated to a greater damage in target organs. However, a limited Treg response may result in the emergence of an effective antiparasite response. Further studies may establish whether boosting tisTregs generation may be useful to limit immunopathology during T. cruzi infection.