Activation of the aryl hidrocarbon receptor (AhR) with TCDD impairs host resistance to Trypanosoma cruzi experimental infection.

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

Mar del plata

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

Aryl hydrocarbon receptor (AhR) is a transcription factor activatedby ligand that is mainly triggered by xenobiotic agents.Increasing evidence suggests that AhR may regulate immunity toinfections. Nevertheless, the role of AhR ligation during infectionsis unclear and unpredictable since it seems to be dependent onseveral factors such as the host-pathogen interactions, the timeof AhR ligation and the particular AhR agonist used. To determinethe role of AhR in the outcome of T.cruzi infection, we studiedthe infection-induced modulation of AhR expression in spleen cellpopulations (SCP) and the effect of the treatment with TCDD (apotent exogenous AhR agonist) on the control of parasite infectionand the modulation of SCP. To assess AhR expression in T. cruziinfection, C57BL/6 mice were infected with 3000 trypomastigotesof T. cruzi and the AhR expression determined in SCP by FACS atdifferent times pi. T. cruzi infection induced, at day 7 pi, a transientand significant up-regulation of AhR expression in CD4+, CD8+and B220+ cells but not in myeloid cell populations. To evaluatethe role of AhR ligation, a group of mice were treated with 40 ug/kg of TCDD (TI, n=7) or vehicle (CI, n=9) one day prior to infectionand monitored for survival, body weight and parasitemia. TCDDtreatment impaired resistance to infection since TI mice showeddecreased survival (p=0.037) and weight gain (p=0.0036) togetherwith increased parasitemias (p=0.013) compared with CI mice.Non-infected TCDD- (TNI, n=5) or vehicle-treated mice (CNI,n=5) did not show significant changes in survival or weight gain.In addition, TI mice showed significantly higher levels of IL-17(p=0.0041) and lower levels of IFN-g (p=0.0085) than CI micein sera. The analysis of SCP at day 15 pi showed that TDCCtreatment was able to reverse the infection-induced reduction ofCD4+ CD25+ Foxp3+ and B220+ cell populations while inducedCD11c+ CD11b- Ly6Chi Ly6G- (pDCs) cell population reduction.Our results show that the outcome of T. cruzi infection could bemodulated by AhR ligation.