CD14 as a Gate Keeper in Microglial Responses to PAMPs and DAMPs

小胶质细胞的哨兵和免疫功能需要对CNS感染和损伤做出快速和充分的反应。Toll样受体（TLR）使细胞能够对这两种威胁做出反应，因为它们能够感知一系列微生物因子以及称为病原体和损伤相关分子模式（PAMP，DAMP）的自衍生因子。我们发现，特别是TLR 4复合物组织了对这些外源性和内源性危险信号的适应性小胶质细胞反应-具有显着的激动剂歧视以及细胞类型和亚群特异性后果。因此，辅助受体CD 14在门控和塑造反应性表型方面表现出了以前未预料到的作用，包括对DAMP的强制支持、防止PAMP挑战中的过度反应以及明显参与小胶质细胞功能的组织。这些贡献不能用激动剂结合的简单辅助来解释。他们认为自己的CD 14信号在决策的位置。我们将讨论CD 14参与的机制和结果，以（i）管理感染和损伤中对PAMP和DAMP的不同小胶质细胞反应，（ii）重点关注TLR 4触发反应中的信号传导控制，（iii）考虑IFNβ在CD 14引导的PAMP和DAMP竞争功能优势中的重要性。

The sentinel and immune functions of microglia require rapid and adequate reactions to CNS infection and damage. Toll-like receptors (TLRs) enable the cells to respond to both threats as they sense a range of microbial agents as well as self-derived factors termed pathogen and damage-associated molecular patterns (PAMPs, DAMPs). We found that especially the TLR4 complex organizes adapted microglial responses to these exogenous and endogenous danger signals―with a remarkable agonist discrimination as well as cell type- and subsetspecific consequences. The coreceptor CD14 thereby demonstrated previously unanticipated roles in gating and shaping the reactive phenotype, including mandatory support for DAMPs, protection against overshooting responses in PAMP challenges and distinct involvement in the organization of microglial functions. These contributions cannot be explained by a simple assistance in agonist binding. They rather suggest own CD14 signaling at a decision-making position. We will address mechanisms and outcomes of CD14 involvement for (i) managing distinct microglial responsiveness to PAMPs and DAMPs in infection and injury, (ii) with a focus on signaling control in TLR4-triggered reactions and (iii) considering the importance of IFNβ in the CD14-guided competition of PAMPs and DAMPs for functional dominance.