ROLE OF IL-33/ST2 AXIS AND TISSUE REPAIR 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

Tucumán

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

Sociedad Argentina de Inmunología

Tissue repair CD4+Foxp3+regulatory T cells (tisTregs) are a specialized Tregsubset that exhibit tissue-specific phenotypic, functional and transcriptionalprofiles. tisTregs display conventional immunoregulatory properties and alsomaintain tissue homeostasis. T. cruzi (Tc) triggers a strong effector responsethat controls parasite spreading but promotes pathological tissue damage. Wepreviously determined that during Tc infection, there is a reduction in tisTregs(ST2+KLRG-1+) frequency and numbers in Blood, Spleen, Liver and SkeletalMuscle (SM) that correlated with decreased systemic levels of their growthfactor IL-33.In this work we aimed to evaluate during Tc infection the correlation betweenthe reduction of tisTregs and evidences of tissue damage and repairmechanisms including biochemical markers of damage and the M1/M2macrophage profile. To this end, Foxp3-GFP C57BL/6 mice were infected with5000 Tc parasites (Tulahuen). Frequencies of tisTregs in Blood, Spleen andLiver inversely correlated with plasmatic levels of GOT, GPT and LDH butdirectly correlated with Glycemia along the infection (p<0.05). Infection affectedmacrophage 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 thatrIL-33 favored the proliferation of ST2+ Tregs in-vitro, increasing thefrequencies of this population in cultures of splenic Tregs cells from infectedand non-infected mice.Our results show that tisTregs are diminished during Tc infection which mayalter M1/M2 activation and tissue repair processes, promoting tissue damage.Exogenous IL-33 may be exploited to increase tisTregs in-vivo to improve tissueintegrity during this infection.