Different responsiveness to AhR ligands of macrophages from B6 and Balb/c mice: Impact on T. cruzi infection

ELIZALDE CARINA; AMBROSIO LAURA FERNANDA; VOLPINI XIMENA; MOTRAN CLAUDIA CRISTINA

Congreso; LXII Reunión Anual de la Sociedad Argentina de Inmunología-SAI.; 2014

Despite being more resistant to T. cruzi infection than BALB/cmice, B6 mice are unable to expand Treg cells populations andshow high mortality due to an imbalance between pro- and antiinflammatorymediators. AhR is a ligand-activated transcriptionfactor that binds xenobiotics that has recently emerged as a criticalphysiological regulator of immune responses affecting bothinnate and adaptive systems. Macrophages (Mo) and dendriticcells activation by TLR-ligands stimulate AhR expression whichis necessary for IDO induction, kynurenines production and Tregand Tr1 cells expansion. AhR signaling can be activated by TCDD(xenobiotic), endogenous agonists like ITE, kynurenines and itis possible that constituents from microorganisms interact withAhR. The polymorphism in AhR system influence responsivenessto AhR ligands. B6 and BALB/c express AhRb-1 and AhRb-2 allelesrespectively, and both strains were classified on the basisof TCDD induced CYP1A1 expression as high responder. Ourhypothesis is that the differential innate immune response andTreg development observed between both mice strains after T.cruzi infection may be influenced by functional polymorphisms ofAhR. Mo from mice of BALB/c and B6 strains were treated withTCDD (160 nM), ITE (100 nM) and T. cruzi lisate (10 ug/ml) for24 h and the expression of Cyp1a1, ahr and ido 1 determinedby qPCR. AhR and ido 1 expression was not affected by differentligands in both mouse strains. As was demonstrated, bothAhR alleles showed similar Cyp1a1 induction by TCDD, whileMo AhRb-2 (Balb/c) stimulated with ITE or T. cruzi showed 2-foldincrease in Cyp1a1 expression compared to Mo AhRb-1 (B6).In addition, Cyp1a1 induced by T. cruzi was inhibited by theaddition of CH223191 (AhR antagonist). Moreover, TCDD andITE induced AhR-dependent secretion of pro-inflammatory (TNFand IL-6) or IL-10 in B6 Mo and Balb/c Mo respectively. Theseresults suggest that the less responsive AhR allele present in B6mice may define the magnitude of the inflammatory responsesand Treg induction during T. cruzi infection.