Department of Biomedicine, Aarhus University, Aarhus, Denmark Aarhus Research Centre for Innate Immunology, Aarhus University, Aarhus, Denmark.
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
EMBO J. 2014 Aug 1;33(15):1654-66. doi: 10.15252/embj.201488029. Epub 2014 Jun 26.
Listeria monocytogenes is a gram-positive facultative intracellular bacterium, which replicates in the cytoplasm of myeloid cells. Interferon β (IFNβ) 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 IFNβ 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 IFNβ expression in human myeloid cells and is sensed to activate a pathway dependent on IFI16, cGAS and STING.
李斯特菌是一种革兰氏阳性兼性细胞内细菌，在髓样细胞的细胞质中复制。干扰素 β（IFNβ）已被报道在李斯特菌病的发病机制中发挥重要作用。尽管在鼠源细胞中的研究提出细菌衍生的环二核苷酸是关键的细菌免疫刺激分子，但在人类髓样细胞中李斯特菌感染期间 IFNβ 表达的机制尚不清楚。在这里，我们报告在人类巨噬细胞中，李斯特菌 DNA 而不是环二核苷酸通过依赖于 DNA 传感器 IFI16 和 cGAS 以及信号适配器分子 STING 的途径刺激 IFN 反应。因此，李斯特菌 DNA 是人类髓样细胞中 IFNβ 表达的主要触发因素，并被感知为激活依赖于 IFI16、cGAS 和 STING 的途径。
