During microbial infection, macrophages link recognition of microbial stimuli to the induction of Type I inflammatory responses. Such inflammatory responses coordinate host defense and pathogen elimination but induce significant tissue damage if sustained, so macrophages are initially activated to induce inflammatory responses but then shift to a tolerant state to suppress inflammatory responses. Macrophage tolerance is regulated by induction of negative regulators of TLR signaling, but its metabolic basis was not known. Here, we review recent studies that indicate that macrophage metabolism changes dynamically over the course of microbial exposure to influence a shift in the inflammatory response. In particular, an initial increase in oxidative metabolism boosts the induction of inflammatory responses, but is followed by a shutdown of oxidative metabolism that contributes to suppression of inflammatory responses. We propose a unifying model for how dynamic changes to oxidative metabolism influences regulation of macrophage inflammatory responses during microbial exposure.

在微生物感染期间，巨噬细胞将微生物刺激的识别与 I 型炎症反应的诱导联系起来。这种炎症反应协调宿主防御和病原体消除，但如果持续会引起显着的组织损伤，因此巨噬细胞最初被激活以诱导炎症反应，但随后转变为耐受状态以抑制炎症反应。巨噬细胞耐受性通过诱导 TLR 信号传导的负调节因子来调节，但其代谢基础尚不清楚。在这里，我们回顾了最近的研究，这些研究表明巨噬细胞代谢在微生物暴露过程中会发生动态变化，从而影响炎症反应的转变。特别是，氧化代谢的初始增加促进了炎症反应的诱导，但随之而来的是有助于抑制炎症反应的氧化代谢的关闭。我们提出了一个统一的模型，说明氧化代谢的动态变化如何影响微生物暴露期间巨噬细胞炎症反应的调节。