Deletion of the aryl hydrocarbon receptor enhances the inflammatory response to Leishmania major infection.

Deletion of the aryl hydrocarbon receptor enhances the inflammatory response to Leishmania major infection.
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DOI:
10.7150/ijbs.7.1220
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发表时间:
2011
影响因子:
9.2
通讯作者:
Vega L
Vega L
中科院分区:
生物学2区
文献类型:
--
作者:
Elizondo G;Rodríguez-Sosa M;Estrada-Muñiz E;Gonzalez FJ;Vega L

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芳烃受体(AhR)是一种配体激活受体,介导环境污染物的毒性,例如2,3,7,8-四氯二苯并-对二恶英(TCDD)。最近,研究表明AhR在免疫和炎症调节中发挥作用。然而,大多数这些研究都是基于外源配体对 AhR 的激活。因此,在本研究中,我们探讨了在缺乏外源配体的情况下该转录因子对利什曼原虫重大感染的免疫反应的作用。我们的结果表明 AhR 失活会导致几种细胞因子水平的改变。与野生型 (wt) 小鼠相比,受感染的 Ahr-null 动物的淋巴结细胞显示 IFNγ 和 IL-12 水平增加,同时 IL-4 和 IL-10 水平下降。与野生型小鼠相比,Ahr 缺失小鼠在寄生虫接种前和感染期间也表现出更高的促炎细胞因子 TNF-α 血清水平。此外,在 Ahr 缺失小鼠中观察到 Treg 细胞数量减少了 30%。这种下降与 Foxp3 mRNA 水平的下降有关。最后,细胞因子谱的改变可以更好地解决大型利斯特菌感染。
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 Treg 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.
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