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LPS inactivation by a host lipase allows lung epithelial cell sensitization for allergic asthma
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 b...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122967/ https://www.ncbi.nlm.nih.gov/pubmed/30021797 http://dx.doi.org/10.1084/jem.20172225 |
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author | Qian, Guojun Jiang, Wei Zou, Benkun Feng, Jintao Cheng, Xiaofang Gu, Jie Chu, Tianqing Niu, Chen He, Rui Chu, Yiwei Lu, Mingfang |
author_facet | Qian, Guojun Jiang, Wei Zou, Benkun Feng, Jintao Cheng, Xiaofang Gu, Jie Chu, Tianqing Niu, Chen He, Rui Chu, Yiwei Lu, Mingfang |
author_sort | Qian, Guojun |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6122967 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-61229672019-03-03 LPS inactivation by a host lipase allows lung epithelial cell sensitization for allergic asthma Qian, Guojun Jiang, Wei Zou, Benkun Feng, Jintao Cheng, Xiaofang Gu, Jie Chu, Tianqing Niu, Chen He, Rui Chu, Yiwei Lu, Mingfang J Exp Med Research Articles 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. Rockefeller University Press 2018-09-03 /pmc/articles/PMC6122967/ /pubmed/30021797 http://dx.doi.org/10.1084/jem.20172225 Text en © 2018 Qian et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Qian, Guojun Jiang, Wei Zou, Benkun Feng, Jintao Cheng, Xiaofang Gu, Jie Chu, Tianqing Niu, Chen He, Rui Chu, Yiwei Lu, Mingfang LPS inactivation by a host lipase allows lung epithelial cell sensitization for allergic asthma |
title | LPS inactivation by a host lipase allows lung epithelial cell sensitization for allergic asthma |
title_full | LPS inactivation by a host lipase allows lung epithelial cell sensitization for allergic asthma |
title_fullStr | LPS inactivation by a host lipase allows lung epithelial cell sensitization for allergic asthma |
title_full_unstemmed | LPS inactivation by a host lipase allows lung epithelial cell sensitization for allergic asthma |
title_short | LPS inactivation by a host lipase allows lung epithelial cell sensitization for allergic asthma |
title_sort | lps inactivation by a host lipase allows lung epithelial cell sensitization for allergic asthma |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122967/ https://www.ncbi.nlm.nih.gov/pubmed/30021797 http://dx.doi.org/10.1084/jem.20172225 |
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