Role of IL-33/ST2 axis and tissue repair regulatory T cells during Trypanosoma cruzi infection

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

Tucumán

Congreso; LXVII Reunión Anual de la Sociedad Argentina de Inmunología; 2019

Sociedad Argentina de Inmunología

Tissue repair CD4+Foxp3+ regulatory T cells (tisTregs) are a specialized Treg subset that exhibit tissue-specific phenotypic, functional and transcriptional profiles. tisTregs display conventional immunoregulatory properties and also maintain tissue homeostasis. T. cruzi (Tc) triggers a strong effector response that controls parasite spreading but promotes pathological tissue damage. We previously determined that during Tc infection, there is a reduction in tisTregs (ST2+KLRG-1+) frequency and numbers in Blood, Spleen, Liver and Skeletal Muscle (SM) that correlated with decreased systemic levels of their growth factor IL-33.In this work we aimed to evaluate during Tc infection the correlation between the reduction of tisTregs and evidences of tissue damage and repair mechanisms including biochemical markers of damage and the M1/M2 macrophage profile. To this end, Foxp3-GFP C57BL/6 mice were infected with 5000 Tc parasites (Tulahuen). Frequencies of tisTregs in Blood, Spleen and Liver inversely correlated with plasmatic levels of GOT, GPT and LDH but directly correlated with Glycemia along the infection (p<0.05). Infection affected macrophage activation leading to an increase in M1 and M2 infiltrate in Spleen (p<0.05) and a decrease in these populations in SM. We finally determined that rIL-33 favored the proliferation of ST2+ Tregs in-vitro, increasing the frequencies of this population in cultures of splenic Tregs cells from infected and non-infected mice.Our results show that tisTregs are diminished during Tc infection which may alter M1/M2 activation and tissue repair processes, promoting tissue damage. Exogenous IL-33 may be exploited to increase tisTregs in-vivo to improve tissue integrity during this infection.