From the Ninth People's Hospital, School of Stomatology and.
the Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200011.
J Biol Chem. 2018 Jan 19;293(3):1030-1039. doi: 10.1074/jbc.M117.805093. Epub 2017 Dec 4.
Type I IFN production and signaling in macrophages play critical roles in innate immune responses. High salt ( high concentrations of NaCl) has been proposed to be an important environmental factor that influences immune responses in multiple ways. However, it remains unknown whether high salt regulates type I IFN production and signaling in macrophages. Here, we demonstrated that high salt promoted IFNβ production and its signaling in both human and mouse macrophages, and consequentially primed macrophages for strengthened immune sensing and signaling when challenged with viruses or viral nucleic acid analogues. Using both pharmacological inhibitors and RNA interference we showed that these effects of high salt on IFNβ signaling were mediated by the p38 MAPK/ATF2/AP1 signaling pathway. Consistently, high salt increased resistance to vesicle stomatitis virus (VSV) infection data indicated that a high-salt diet protected mice from lethal VSV infection. Taken together, these results identify high salt as a crucial regulator of type I IFN production and signaling, shedding important new light on the regulation of innate immune responses.
I 型干扰素（IFN）在巨噬细胞中的产生和信号转导在先天免疫反应中起着至关重要的作用。高盐（高浓度的 NaCl）已被提出是一种重要的环境因素，以多种方式影响免疫反应。然而，目前尚不清楚高盐是否调节巨噬细胞中 I 型 IFN 的产生和信号转导。在这里，我们证明高盐促进了人源和鼠源巨噬细胞中 IFNβ 的产生及其信号转导，并在受到病毒或病毒核酸类似物的刺激时，使巨噬细胞为增强的免疫感应和信号转导做好了准备。我们使用药理学抑制剂和 RNA 干扰证明了高盐对 IFNβ 信号转导的这些影响是通过 p38 MAPK/ATF2/AP1 信号通路介导的。一致地，高盐增加了对水疱性口炎病毒（VSV）感染的抵抗力。数据表明，高盐饮食可保护小鼠免受致死性 VSV 感染。总之，这些结果表明高盐是 I 型 IFN 产生和信号转导的关键调节剂，为先天免疫反应的调节提供了重要的新视角。
