STUDY OF THE ROLE OF TISSUE RESIDENT REGULATORY T CELLS DURING TRYPANOSOMA CRUZI INFECTION

SANTIAGO BOCCARDO; CINTIA ARAUJO FURLAN; CONSTANZA RODRIGUEZ; CAROLINA ABRATE; LAURA ALMADA; ADRIANA GRUPPI; CAROLINA LUCÍA MONTES; EVA VIRGINIA ACOSTA RODRÍGUEZ

Mar del Plata

Congreso; Reunión Conjunta SAI . SAIC . SAFIS; 2018

During T. cruzi (Tc) infection, a limited CD4+Foxp3+ regulatory T cells (Tregs) response allows the induction of protective CD8+ T cell immunity in peripheral tissues, but it may also facilitate tissue damage and immunopathology.  Tissue  resident  Tregs  (tisTregs)  are  a  specialized subset that, besides regulating effector cells, maintains tissue homeostasis. We previously showed that Tc infected mice exhibit a reduced frequency of Tregs, particularly of those expressing the tisTregs markers ST2 and KLRG1, in Blood, Spleen, Liver and Skeletal Muscle (SM). Our current aim is to evaluate concentration of tisTregsgrowth factors during Tc infection and the role of TisTregs in the regulation of effector immune responses and immunopathology. To this end, Foxp3-GFP-C57BL/6 mice infected with 5000 Tc parasites (Tulahuen) were used as infection model. The levels of IL-33 and IL-18,recognized tisTregs growth factors, were determined by ELISA in plasma, and Spleen and SM lysates. IL-33 levels decreased and IL-18 levels increased after 14 and 21 dpi in plasma and spleen, but both cytokines increased after 21dpi in SM (p<0.05). Next, we evaluated by flow cytometry the frequency of Tregs, tisTregs and parasite-specific CD8+ T cells in Blood, Spleen, Liver and SM. We found  a  significant  inverse  correlation  between  the  frequencies of Tregs, but not tisTregs, with parasite-specific CD8+ T cells in blood, spleen and liver (p<0.001). Finally, we determined that several biochemical markers of damage (LDH, GOT, GPT, CK and CK-MB activities) were increased in plasma at 21dpi, corresponding withthe lowest frequencies of Tregs and tisTregs. These results suggest that tisTregs and Tregs responses may be restrained during Tc infection, favoring the emergence of an effective antiparasite response but also promoting agreater damage in target organs. Further studies may establish whether boosting tisTregs generation may be useful to limit immunopathology during T. cruzi infection.