ACTIVATION OF THE ARYL HYDROCARBON RECEPTOR (AHR) WITH TCDD IMPAIRS HOST RESISTANCE TO TRYPANOSOMA CRUZI EXPERIMENTAL INFECTION

AMBROSIO, LF; VOLPINI, XIMENA; ELIZALDE, C; MOTRAN, CLAUDIA CRISTINA

Mar del Plata

Congreso; LXII Reunión científica de la Sociedad Argentina de Inmunología y LIX REUNIÓN CIENTÍFICA ANUAL Sociedad Argentina de Investigación Clínica; 2014

SAI-SAIC

Aryl hydrocarbon receptor (AhR) is a transcription factor activated by ligand that is mainly triggered by xenobiotic agents. Increasing evidence suggests that AhR may regulate immunity to infections. Nevertheless, the role of AhR ligation during infections is unclear and unpredictable since it seems to be dependent on several factors such as the host-pathogen interactions, the time of AhR ligation and the particular AhR agonist used. To determine the role of AhR in the outcome of T.cruzi infection, we studied the infection-induced modulation of AhR expression in spleen cell populations (SCP) and the effect of the treatment with TCDD (a potent exogenous AhR agonist) on the control of parasite infection and the modulation of SCP. To assess AhR expression in T. cruzi infection, C57BL/6 mice were infected with 3000 trypomastigotes of T. cruzi and the AhR expression determined in SCP by FACS at different times pi. T. cruzi infection induced, at day 7 pi, a transient and significant up-regulation of AhR expression in CD4+, CD8+ and B220+ cells but not in myeloid cell populations. To evaluate the 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 infection and monitored for survival, body weight and parasitemia. TCDD treatment impaired resistance to infection since TI mice showed decreased survival (p=0.037) and weight gain (p=0.0036) together with 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 mice in sera. The analysis of SCP at day 15 pi showed that TDCC treatment was able to reverse the infection-induced reduction of CD4+ CD25+ Foxp3+ and B220+ cell populations while induced CD11c+ CD11b- Ly6Chi Ly6G- (pDCs) cell population reduction. Our results show that the outcome of T. cruzi infection could be modulated by AhR ligation