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Int J Biol Sci 2011; 7(9):1220-1229. doi:10.7150/ijbs.7.1220 This issue Cite

Research Paper

Deletion of the Aryl Hydrocarbon Receptor Enhances the Inflammatory Response to Leishmania major Infection

Guillermo Elizondo¹, Miriam Rodríguez-Sosa², Elizabet Estrada-Muñiz³, Frank J. Gonzalez⁴, Libia Vega^{3 ✉}

1. Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional. Departamento de Biología Celular. Av. IPN 2508. San Pedro Zacatenco. C. P. 07360, México D. F., México.
2. Facultad de Estudios Superiores-Iztacala, UNAM. Unidad de Biomedicina, C.P. 54090, Tlalnepantla, Estado de México, México.
3. Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional. Departamento de Toxicología. Av. IPN 2508. San Pedro Zacatenco. C. P. 07360, México D. F., México.
4. Laboratory of Metabolism, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA.

✉ Corresponding author: Libia Vega; Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional. Departamento de Toxicología. Av. IPN 2508. San Pedro Zacatenco. C. P. 07360. México D. F., México. Phone +52-55-5747-3800 ext. 5472. Fax +52-55-5747-3395. E-mail: lvegamx More

Abstract

The aryl hydrocarbon receptor (AhR) is a ligand-activated receptor that mediates the toxicity of environmental pollutants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Recently, it has been shown that the AhR plays a role in immune and inflammatory regulation. However, most of these studies are based on the activation of AhR by exogenous ligands. Therefore, in the present study, we addressed the role of this transcription factor, in the absent of exogenous ligand, on the immune response to Leishmania major infection. Our results indicate that inactivation of the AhR results in an alteration of the levels of several cytokines. Lymph node cells from infected Ahr-null animals displayed an increase in IFNγ and IL-12 levels, together with a decrease in IL-4 and IL-10 levels compared to wild-type (wt) mice. Ahr-null mice also presented higher serum levels of the pro-inflammatory cytokine TNF-α prior to parasite inoculation and during infection compared to wt mice. Moreover, a 30% decrease in the population of T_reg cells was observed in Ahr-null mice. This decrease was associated with a reduction in Foxp3 mRNA levels. Finally, the alteration in the cytokine profile results in a better resolution of the L. major infection.

Keywords: Aryl hydrocarbon receptor, Inflammatory response, Regulatory T cells, Leishmania major

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