Role of the aryl hydrocarbon receptor (AhR) in the control of Trypanosoma cruzi experimental infection.

AMBROSIO, LAURA FERNANDA; ELIZALDE, CARINA; ALTAMIRANO, ANDRES; CERVI, LAURA; MOTRAN, CLAUDIA CRISTINA

Congreso; LXI Reunión Científica Anual De La Sociedad Argentina De Inmunología; 2013

Indoleamine 2,3 dioxigenase activity is critical for host resistance against T. cruzi infection. The administration of 3-Hydroxy Kynurenine (3-HK) (one of the kynurenines produced by IDO) to mice during the acute phase of the infection decreases the parasitemia and the inflammatory pathology improving their survival. Recently it was demonstrated that 3-HK is a ligand of the aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor that participates in the induction of IDO in dendritic cells (DC) and macrophages (Mo). To evaluate the expression of AhR during experimental T. cruzi infection, BALB/c mice were infected with 500 tp of T. cruzi and the AhR expression was determined in spleen mononuclear cells (SMC) by Quantitative Real Time PCR (qPCR), Western Blot and flow cytometry at different times pi. T. cruzi infection induced, at day 7 pi, a transient and significant upregulation of AhR transcript while the AhR protein expression was evident in SMC (T, DC and Mo) at the parasitemia peak (day 17 pi). To evaluate the role of AhR in the control of the parasite replication in vivo, a group of mice were daily treated with the AhR antagonist CH223191 (2.5 mg/dia/Kg) (TG, n=5) in corn oil or vehicle (CG, n=5) from the beginning of the infection. The inhibition of AhR signaling reduced significantly the resistance to the infection since the TG mice showed higher parasitemias than the CG mice (p