Robertson Kevin A, Ghazal Peter
Division of Infection and Pathway Medicine, University of Edinburgh , Edinburgh , UK.
Front Immunol. 2016 Dec 23;7:634. doi: 10.3389/fimmu.2016.00634. eCollection 2016.
The sterol metabolic network is emerging center stage in inflammation and immunity. Historically, observational clinical studies show that hypocholesterolemia is a common side effect of interferon (IFN) treatment. More recently, comprehensive systems-wide investigations of the macrophage IFN response reveal a direct molecular link between cholesterol metabolism and infection. Upon infection, flux through the sterol metabolic network is acutely moderated by the IFN response at multiple regulatory levels. The precise mechanisms by which IFN regulates the mevalonate-sterol pathway-the spine of the network-are beginning to be unraveled. In this review, we discuss our current understanding of the multifactorial mechanisms by which IFN regulates the sterol pathway. We also consider bidirectional communications resulting in sterol metabolism regulation of immunity. Finally, we deliberate on how this fundamental interaction functions as an integral element of host protective responses to infection and harmful inflammation.
甾醇代谢网络正在炎症和免疫领域崭露头角。从历史上看，观察性临床研究表明，低胆固醇血症是干扰素（IFN）治疗的常见副作用。最近，对巨噬细胞IFN反应进行的全面全系统研究揭示了胆固醇代谢与感染之间的直接分子联系。感染后，甾醇代谢网络的通量在多个调节水平上被IFN反应急剧调节。IFN调节甲羟戊酸-甾醇途径（该网络的核心）的精确机制正开始被揭示。在这篇综述中，我们讨论了目前对IFN调节甾醇途径的多因素机制的理解。我们还考虑了导致免疫的甾醇代谢调节的双向通信。最后，我们思考这种基本相互作用如何作为宿主对感染和有害炎症的保护性反应的一个组成部分发挥作用。
