TRYPANOSOMA CRUZI INFECTION: A NOVEL TREATMENT WITH ENDOGENOUS NONTOXIC AHR LIGANDS PROMOTES TREG CELLS DIFFERENTIATION WITHOUT DETRIMENTAL EFFECTS ON PARASITE SPECIFIC IMMUNITY.

VOLPINI, XIMENA; INSFRAN, CONSTANZA; MOTRAN, CC; CERVI, LAP; AMBROSIO, LF; POSTAM, MIRIAM

Mar del Plata

Congreso; LXI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC) LXIV REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI); 2016

SAIC-SAI

During T. cruzi infection, both a strong inflammatory and anefficient regulatory responses are essential to restrict parasite replicationand prevent immunopathology. Studies in T. cruzi-infectedB6 mice have shown that despite its ability to control parasitereplication they are unable to expand regulatory T cells (Treg),resulting in the premature death of these animals by inflammatoryliver failure. The AhR is a ligand-activated transcription fact or thatplays important roles in several biological processes, including theimmune response. In T cells, its function depends on the ligandbound with the xenobiotic TCDD and endogenous agonist ITE andkynurenines promoting Treg and FICZ favoring Th17 differentiation.We have reported that the treatment of B6 mice with TCDD24hs prior infection was able to control the inflammatory responseincreasing the% of Treg but also inducing T cell apoptosis, botheffects contribute to increase the parasite burden and to diminishthe survival. In this study we tested the hypothesis that the a ctivationof AhR signaling using two endogenous nontoxic AhR ligandsas ITE and 3-HK (a kynurenine toxic for T. cruzi) might controlthe infection and also the immunopathology. The treatment of T.cruzi-infected B6 mice with ITE (days 7, 9 and 11 post infection(pi)) plus 3-HK (from day 5 to 10 pi) induced a significant incr easein the% (day 13, p