Wajant Harald, Siegmund Daniela
Division of Molecular Internal Medicine, Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.
Front Cell Dev Biol. 2019 May 29;7:91. doi: 10.3389/fcell.2019.00091. eCollection 2019.
Macrophages stand in the first line of defense against a variety of pathogens but are also involved in the maintenance of tissue homeostasis. To fulfill their functions macrophages sense a broad range of pathogen- and damage-associated molecular patterns (PAMPs/DAMPs) by plasma membrane and intracellular pattern recognition receptors (PRRs). Intriguingly, the overwhelming majority of PPRs trigger the production of the pleiotropic cytokine tumor necrosis factor-alpha (TNF). TNF affects almost any type of cell including macrophages themselves. TNF promotes the inflammatory activity of macrophages but also controls macrophage survival and death. TNF exerts its activities by stimulation of two different types of receptors, TNF receptor-1 (TNFR1) and TNFR2, which are both expressed by macrophages. The two TNF receptor types trigger distinct and common signaling pathways that can work in an interconnected manner. Based on a brief general description of major TNF receptor-associated signaling pathways, we focus in this review on research of recent years that revealed insights into the molecular mechanisms how the TNFR1-TNFR2 signaling network controls the life and death balance of macrophages. In particular, we discuss how the TNFR1-TNFR2 signaling network is integrated into PRR signaling.
巨噬细胞处于抵御多种病原体的第一道防线，但也参与维持组织稳态。为履行其功能，巨噬细胞通过质膜和细胞内模式识别受体（PRR）感知多种病原体相关分子模式（PAMP）和损伤相关分子模式（DAMP）。有趣的是，绝大多数PRR会触发多效性细胞因子肿瘤坏死因子-α（TNF）的产生。TNF几乎影响任何类型的细胞，包括巨噬细胞自身。TNF促进巨噬细胞的炎症活性，但也控制巨噬细胞的存活和死亡。TNF通过刺激两种不同类型的受体发挥其作用，即TNF受体-1（TNFR1）和TNFR2，巨噬细胞均可表达这两种受体。这两种TNF受体类型触发不同但又相互关联的信号通路。基于对主要TNF受体相关信号通路的简要概述，我们在本综述中重点关注近年来的研究，这些研究揭示了TNFR1 - TNFR2信号网络如何控制巨噬细胞生死平衡的分子机制。特别是，我们讨论了TNFR1 - TNFR2信号网络如何整合到PRR信号传导中。
