LPS inactivation by a host lipase allows lung epithelial cell sensitization for allergic asthma.
LPS inactivation by a host lipase allows lung epithelial cell sensitization for allergic asthma.
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宿主脂肪酶使 LPS 失活，使肺上皮细胞对过敏性哮喘敏感
DOI：
10.1084/jem.20172225
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发表时间：
2018-09-03
期刊：
影响因子：
--
通讯作者：
Lu M
中科院分区：
文献类型：
--
作者：
Qian G;Jiang W;Zou B;Feng J;Cheng X;Gu J;Chu T;Niu C;He R;Chu Y;Lu M
过敏性哮喘是一种主要由Th 2免疫机制介导的慢性炎症性疾病。大量研究表明，生命早期暴露于脂多糖（LPS）与过敏性哮喘呈负相关。一种提出的机制引起肺上皮细胞对LPS的脱敏。我们在这里报告，酰氧酰基水解酶（AOAH），宿主脂肪酶，降解和灭活LPS，使小鼠更容易受到屋尘螨（HDM）诱导的过敏性哮喘。来自Aoah−/−小鼠的肺上皮细胞对HDM刺激不敏感，降低了树突状细胞活化和Th 2应答。抗生素治疗减少了直肠内产生LPS的细菌，使对HDM的Aoah−/−反应正常化，而直肠内给予LPS则改善了哮喘。Aoah−/−小鼠的粪便、血浆和肺部比Aoah+/+小鼠含有更多的生物活性LPS。通过灭活肺内LPS，AOAH因此防止肺上皮细胞的脱敏。一种预防革兰氏阴性细菌性肺炎中严重肺部炎症/损伤的酶似乎具有诱发Th 2介导的气道疾病的自相矛盾的作用。
Allergic asthma is a chronic inflammatory disease primarily mediated by Th2 immune mechanisms. Numerous studies have suggested that early life exposure to lipopolysaccharide (LPS) is negatively associated with allergic asthma. One proposed mechanism invokes desensitization of lung epithelial cells by LPS. We report here that acyloxyacyl hydrolase (AOAH), a host lipase that degrades and inactivates LPS, renders mice more susceptible to house dust mite (HDM)–induced allergic asthma. Lung epithelial cells from Aoah−/− mice are refractory to HDM stimulation, decreasing dendritic cell activation and Th2 responses. Antibiotic treatment that diminished commensal LPS-producing bacteria normalized Aoah−/− responses to HDM, while giving LPS intrarectally ameliorated asthma. Aoah−/− mouse feces, plasma, and lungs contained more bioactive LPS than did those of Aoah+/+ mice. By inactivating commensal LPS, AOAH thus prevents desensitization of lung epithelial cells. An enzyme that prevents severe lung inflammation/injury in Gram-negative bacterial pneumonia has the seemingly paradoxical effect of predisposing to a Th2-mediated airway disease.
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