气候变化领域集成服务门户(CCPortal): Inactivation of common airborne antigens by perfluoroalkyl chemicals modulates early life allergic asthma

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DOI	10.1073/pnas.2011957118
	Inactivation of common airborne antigens by perfluoroalkyl chemicals modulates early life allergic asthma
	Wang M.; Li Q.; Hou M.; Chan L.L.Y.; Liu M.; Ter S.K.; Dong T.; Xia Y.; Chotirmall S.H.; Fang M.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:24
英文摘要	Allergic asthma, driven by T helper 2 cell-mediated immune responses to common environmental antigens, remains the most common respiratory disease in children. Perfluorinated chemicals (PFCs) are environmental contaminants of great concern, because of their wide application, persistence in the environment, and bio-accumulation. PFCs associate with immunological disorders including asthma and attenuate immune responses to vaccines. The influence of PFCs on the immunological response to allergens during childhood is unknown. We report here that a major PFC, perfluorooctane sulfonate (PFOS), inactivates house dust mite (HDM) to dampen 5-wk-old, early weaned mice from developing HDM-induced allergic asthma. PFOS further attenuates the asthma protective effect of the microbial product lipopolysaccharide (LPS). We demonstrate that PFOS prevents desensitization of lung epithelia by LPS, thus abolishing the latter’s protective effect. A close mechanistic study reveals that PFOS specifically binds the major HDM allergen Der p1 with high affinity as well as the lipid A moiety of LPS, leading to the inactivation of both antigens. Moreover, PFOS at physiological human (nanomolar) concentrations inactivates Der p1 from HDM and LPS in vitro, although higher doses did not cause further inactivation because of possible formation of PFOS aggregates. This PFOS-induced neutralization of LPS has been further validated in primary human cell models and extended to an in vivo bacterial infection mouse model. This study demonstrates that early life exposure of mice to a PFC blunts airway antigen bioactivity to modulate pulmonary inflammatory responses, which may adversely affect early pulmonary health. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Early life exposure; House dust mites; Lipopolysaccharide; Perfluorinated chemicals; Pulmonary immunomodulation
语种	英语
scopus关键词	cysteine proteinase; Der p1 allergen; Escherichia coli lipopolysaccharide; house dust allergen; lipid A; perfluorooctanesulfonic acid; unclassified drug; airborne particle; allergic asthma; animal cell; animal experiment; animal model; animal tissue; antigen binding; Article; binding affinity; biological activity; concentration (parameter); controlled study; Dermatophagoides; desensitization; disease course; disease model; environmental exposure; female; human; human cell; immune response; immunogenicity; immunomodulation; in vitro study; in vivo study; lung epithelium; lung infection; mouse; mouse model; nonhuman; pneumonia; primary cell; Pseudomonas infection; validation study
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/238525
作者单位	School of Civil and Environmental Engineering, Nanyang Technological University, Singapore, 639798, Singapore; Key Laboratory of Environmental Nanotechnology and Health Effects, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; School of Ecological Technology and Engineering, Shanghai Institute of Technology, Shanghai, 201418, China; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 639798, Singapore
推荐引用方式 GB/T 7714	Wang M.,Li Q.,Hou M.,et al. Inactivation of common airborne antigens by perfluoroalkyl chemicals modulates early life allergic asthma[J],2021,118(24).
APA	Wang M..,Li Q..,Hou M..,Chan L.L.Y..,Liu M..,...&Fang M..(2021).Inactivation of common airborne antigens by perfluoroalkyl chemicals modulates early life allergic asthma.Proceedings of the National Academy of Sciences of the United States of America,118(24).
MLA	Wang M.,et al."Inactivation of common airborne antigens by perfluoroalkyl chemicals modulates early life allergic asthma".Proceedings of the National Academy of Sciences of the United States of America 118.24(2021).