Dynamic changes in macrophage metabolism modulate induction and suppression of Type I inflammatory responses.
Dynamic changes in macrophage metabolism modulate induction and suppression of Type I inflammatory responses.
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DOI：
10.1016/j.coi.2021.07.012
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发表时间：
2021-08
影响因子：
7
通讯作者：
Haoming Luan;T. Horng
中科院分区：
文献类型：
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作者：
Haoming Luan;T. Horng
必须调节炎症反应的诱导和抑制，以平衡有益和有害的影响。从合成代谢到分解代谢的动态转变调节了炎症反应从诱导到抑制的转变。炎症反应的诱导是由高能量的合成代谢状态和增强的氧化代谢引起的。氧化代谢和分解代谢状态的降低促进了炎症反应的抑制。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，但如果持续下去，会导致严重的组织损伤，因此巨噬细胞最初被激活以诱导炎症反应，然后转移到耐受状态以抑制炎症反应。巨噬细胞耐受是通过诱导TLR信号负调节因子来调节的，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动态变化，从而影响炎症反应的转变。特别是，最初氧化代谢的增加促进了炎症反应的诱导，但随后氧化代谢的关闭有助于抑制炎症反应。我们提出了一个统一的模型，如何在微生物暴露过程中氧化代谢的动态变化影响巨噬细胞炎症反应的调节。
HighlightsInduction and suppression of inflammatory responses must be regulated to balance beneficial and detrimental effects.A dynamic shift from anabolic to catabolic metabolism modulates the shift from induction to suppression of inflammatory responses.Induction of inflammatory responses is fueled by a high-energy anabolic state and enhanced oxidative metabolism.Suppression of inflammatory responses is facilitated by a decreased oxidative metabolism and a catabolic state.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.