Laboratory of Clinical Immunology and Microbiology, NIAID, National Institutes of Health, Bethesda, Maryland, USA.
Inflammation Program, University of Iowa, Iowa City, Iowa, USA.
J Biol Chem. 2020 Dec 18;295(51):17842-17851. doi: 10.1074/jbc.REV120.015254.
Animals can sense the presence of microbes in their tissues and mobilize their own defenses by recognizing and responding to conserved microbial structures (often called microbe-associated molecular patterns (MAMPs)). Successful host defenses may kill the invaders, yet the host animal may fail to restore homeostasis if the stimulatory microbial structures are not silenced. Although mice have many mechanisms for limiting their responses to lipopolysaccharide (LPS), a major Gram-negative bacterial MAMP, a highly conserved host lipase is required to extinguish LPS sensing in tissues and restore homeostasis. We review recent progress in understanding how this enzyme, acyloxyacyl hydrolase (AOAH), transforms LPS from stimulus to inhibitor, reduces tissue injury and death from infection, prevents prolonged post-infection immunosuppression, and keeps stimulatory LPS from entering the bloodstream. We also discuss how AOAH may increase sensitivity to pulmonary allergens. Better appreciation of how host enzymes modify LPS and other MAMPs may help prevent tissue injury and hasten recovery from infection.
动物能够感知组织中微生物的存在，并通过识别和响应保守的微生物结构（通常称为微生物相关分子模式（MAMPs））来动员自身的防御机制。成功的宿主防御可能会杀死入侵者，但如果刺激微生物结构没有沉默，宿主动物可能无法恢复体内平衡。尽管小鼠有许多限制其对脂多糖（LPS）反应的机制，LPS 是一种主要的革兰氏阴性细菌 MAMP，但需要高度保守的宿主脂肪酶来消除组织中 LPS 的感应并恢复体内平衡。我们回顾了最近在理解这种酶，酰氧基酰基水解酶（AOAH），如何将 LPS 从刺激物转化为抑制剂，减少感染引起的组织损伤和死亡，防止感染后长期免疫抑制以及阻止刺激 LPS 进入血液方面的进展。我们还讨论了 AOAH 如何增加对肺部过敏原的敏感性。更好地了解宿主酶如何修饰 LPS 和其他 MAMPs 可能有助于预防组织损伤并加速从感染中恢复。
