ROLE OF THE ARYL HIDROCARBON RECEPTOR (AHR) IN THE CONTROL OF TRYPANOSOMA CRUZI EXPERIMENTAL INFECTION

. ELIZALDE, CARINA; ; AMBROSIO, LAURA.;; ; KNUBEL, CAROLINA; ; CERVI, LAURA; ; MOTRAN, CLAUDIA C

Congreso; XLI Reunion Anual de la Sociedad Argentina de Inmunologia; 2013

SAI

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<0.05). In addition, when the role of AhR in the control of the intracellular parasite replication in DC and Mo was studied in vitro, we observed that the blockade of AhR signaling result in a stimulatory effect on intracellular parasite growth. Our results show evidence for the participation of AhR signaling in the control of T. cruzi replication.