Aryl hydrocarbon receptor protects against bacterial infection by promoting macrophage survival and reactive oxygen species production
Aryl hydrocarbon receptor protects against bacterial infection by promoting macrophage survival and reactive oxygen species production
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DOI：
10.1093/intimm/dxt067
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发表时间：
2014-04-01
影响因子：
4.4
通讯作者：
Yoshimura, Akihiko
中科院分区：
文献类型：
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作者：
Kimura, Akihiro;Abe, Hiromi;Yoshimura, Akihiko
AhR 通过增强巨噬细胞存活和 ROS 产生来防止李斯特菌感染。芳基碳氢化合物受体 (AhR) 对于各种免疫反应至关重要。 AhR 与细胞内细菌单核细胞增生李斯特菌 (LM) 感染之间的关系知之甚少。在这里，我们发现，为了应对 LM 感染，AhR 是通过促进巨噬细胞存活和活性氧 (ROS) 产生来清除细菌所必需的。 AhR 缺陷的小鼠更容易感染李斯特菌病，而 AhR 缺陷会促进体内和体外细菌的生长。另一方面，尽管AhR缺陷型小鼠对LM感染的易感性增强，但感染LM的AhR缺陷型巨噬细胞中促炎细胞因子增加。随后的研究表明，AhR 通过诱导抗凋亡因子（巨噬细胞凋亡抑制剂）来防止 LM 感染引起的巨噬细胞死亡，从而促进巨噬细胞在 LM 感染情况下的存活。此外，AhR 还能促进 ROS 的产生，从而清除细菌。我们的结果表明，AhR 对于抵抗 LM 感染至关重要，因为它可以促进巨噬细胞存活和 ROS 产生。这表明 AhR 通过其配体激活可能是对抗李斯特菌病的有效策略。
The AhR protects against Listeria infection by enhancing macrophage survival and ROS production.Aryl hydrocarbon receptor (AhR) is crucial for various immune responses. The relationship between AhR and infection with the intracellular bacteria Listeria monocytogenes (LM) is poorly understood. Here, we show that in response to LM infection, AhR is required for bacterial clearance by promoting macrophage survival and reactive oxygen species (ROS) production. AhR-deficient mice were more susceptible to listeriosis, and AhR deficiency enhances bacterial growth in vivo and in vitro. On the other hand, pro-inflammatory cytokines were increased in AhR-deficient macrophages infected with LM despite enhanced susceptibility to LM infection in AhR-deficient mice. Subsequent studies demonstrate that AhR protects against macrophage cell death induced by LM infection through the induction of the antiapoptotic factor, the apoptosis inhibitor of macrophages, which promotes macrophage survival in the setting of LM infection. Furthermore, AhR promotes ROS production for bacterial clearance. Our results demonstrate that AhR is essential to the resistance against LM infection as it promotes macrophage survival and ROS production. This suggests that the activation of AhR by its ligands may be an effective strategy against listeriosis.