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

S BOCCARDO; CL ARAUJO FURLAN; C RODRIGUEZ; L ALMADA; CP ABRATE; CL MONTES; A GRUPPI; EV ACOSTA RODRIGUEZ

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Tissue resident CD4+Foxp3+ regulatory T cells (tTregs) have emerged as a specialized Treg subset that exhibit phenotypic, funtional and transcriptional profiles particular to each tissue. tTregs not only regulate immune effector function as lymphoid Tregs but also modulate several non-immune biological processes and maintain tissue homeostasis. T. cruzi (Tc) triggers a strong effector response that controls parasite spreading and may promote tissue damage and immune pathology. Our previous results showed that Tc infection is linked to a limited Tregs response that is required for the emergence of protective CD8+ T cell immunity.Our current aim is to evaluate whether tTregs plays any role in the regulation of tissue damage and pathogenesis in Chagas disease. To this end, Foxp3-GFP C57BL/6 mice were infected with 5000 Tc parasites (Tulahuen) and frequency and phenotype of Tregs were determined by flow cytometry in blood and spleen as well as in target tissues such as liver (L), skeletal muscle (SM) and heart (H) at different days post-infection (dpi). As reported in blood and spleen, the frequency of Tregs identified as CD4+Foxp3-GFP+ T cells decreased in L, SM and H along the infection. We next evaluated the expression of IL-18R and ST2, required for survival and considered markers of tTregs. Tc infection did not change the % of either IL- 18R+ Tregs in any organ or ST2+ Tregs in spleen but it reduced % of ST2+ Tregs in L and SM. Finally, we studied whether Tc infection triggered the production of tTregs growth factors such as IL-33. We determined by ELISA that while IL-33 was detectable at low concentration in the plasma of non-infected mice, it became undetectable after 14 and 21 dpi (p<0.001). Our preliminary results suggest that tTregs are not induced during Tc infection and this may be associated to a greater damage in target organs. Further studies may establish whether boosting tTregs generation may be useful to limit immunopathology during Tc infection.