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

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

Congreso; SAIC-SAI-SAFIS 2018.; 2018

During T. cruzi (Tc) infection, a limited CD4+Foxp3+ regulatoryT cells (Tregs) response allows the induction ofprotective CD8+ T cell immunity in peripheral tissues, butit may also facilitate tissue damage and immunopathology.Tissue resident Tregs (tisTregs) are a specializedsubset that, besides regulating effector cells, maintainstissue homeostasis. We previously showed that Tc infectedmice exhibit a reduced frequency of Tregs, particularlyof those expressing the tisTregs markers ST2 and KLRG-1, 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 TisTregsin the regulation of effector immune responses and immunopathology.To this end, Foxp3-GFP-C57BL/6 miceinfected with 5000 Tc parasites (Tulahuen) were usedas infection model. The levels of IL-33 and IL-18, recognizedtisTregs growth factors, were determined by ELISAin plasma, and Spleen and SM lysates. IL-33 levels decreasedand IL-18 levels increased after 14 and 21 dpiin plasma and spleen, but both cytokines increased after21dpi in SM (p<0.05). Next, we evaluated by flow cytometrythe frequency of Tregs, tisTregs and parasite-specificCD8+ T cells in Blood, Spleen, Liver and SM. Wefound a significant inverse correlation between the frequenciesof Tregs, but not tisTregs, with parasite-specificCD8+ T cells in blood, spleen and liver (p<0.001).Finally, we determined that several biochemical markersof damage (LDH, GOT, GPT, CK and CK-MB activities)were increased in plasma at 21dpi, corresponding withthe lowest frequencies of Tregs and tisTregs. These resultssuggest that tisTregs and Tregs responses may berestrained during Tc infection, favoring the emergence ofan effective antiparasite response but also promoting agreater damage in target organs. Further studies mayestablish whether boosting tisTregs generation may beuseful to limit immunopathology during T. cruzi infection.