Listeria monocytogenes induces IFNβ expression through an IFI16-, cGAS- and STING-dependent pathway
Listeria monocytogenes induces IFNβ expression through an IFI16-, cGAS- and STING-dependent pathway
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DOI：
10.15252/embj.201488029
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发表时间：
2014-08-01
期刊：
影响因子：
11.4
通讯作者：
Paludan, Soren R.
中科院分区：
文献类型：
--
作者：
Hansen, Kathrine;Prabakaran, Thaneas;Paludan, Soren R.
单核细胞增生李斯特菌是一种革兰氏阳性兼性胞内细菌，在骨髓细胞的细胞质中复制。据报道，干扰素β（IFN β）在李斯特菌病的潜在机制中发挥重要作用。尽管在小鼠细胞中的研究已经提出细菌衍生的环状二AMP是关键的细菌免疫刺激分子，但是在L.人骨髓细胞中的单核细胞增多症感染仍然未知。在这里，我们报告说，在人类巨噬细胞中，李斯特菌DNA而不是环状二AMP通过依赖于DNA传感器IFI16和cGAS以及信号衔接分子STING的途径刺激IFN应答。因此，李斯特菌DNA是人类骨髓细胞中IFN β表达的主要触发因素，并被感知激活依赖于IFI16、cGAS和STING的途径。
Listeria monocytogenes is a gram-positive facultative intracellular bacterium, which replicates in the cytoplasm of myeloid cells. Interferon beta (IFN beta) has been reported to play an important role in the mechanisms underlying Listeria disease. Although studies in murine cells have proposed the bacteria-derived cyclic-di-AMP to be the key bacterial immunostimulatory molecule, the mechanism for IFN beta expression during L. monocytogenes infection in human myeloid cells remains unknown. Here we report that in human macrophages, Listeria DNA rather than cyclic-di-AMP is stimulating the IFN response via a pathway dependent on the DNA sensors IFI16 and cGAS as well as the signalling adaptor molecule STING. Thus, Listeria DNA is a major trigger of IFN beta expression in human myeloid cells and is sensed to activate a pathway dependent on IFI16, cGAS and STING.