LPS inactivation by a host lipase allows lung epithelial cell sensitization for allergic asthma

The Journal of Experimental Medicine
Guojun QianMingfang Lu

Abstract

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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Citations

Sep 11, 2019·Nature Immunology·Tomasz P WypychBenjamin J Marsland
Jan 8, 2020·Bio-protocol·Clara Jana-Lui BuschMichael H Sieweke
Nov 2, 2019·Internal and Emergency Medicine·Alessio FabbrizziGiovanni Fontana
Oct 16, 2020·Cellular and Molecular Life Sciences : CMLS·Anna CiesielskaKatarzyna Kwiatkowska
Feb 26, 2021·Microbiology and Immunology·Qunzhi WangHua Zhou
May 7, 2021·The Journal of Allergy and Clinical Immunology·Meng ZhangZhenwei Xia
Jun 9, 2021·Proceedings of the National Academy of Sciences of the United States of America·Mengjing WangMingliang Fang
Sep 4, 2021·Journal of Medicinal Chemistry·Zhicheng XieYouhong Hu

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Methods Mentioned

BETA
bronchoalveolar lavage
ELISA
flow cytometry
PCR
FACS

Software Mentioned

TreeStar
PRISM
Trimmomatic
FLASH
UPARSE
GraphPad
Flow Jo

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