气候变化领域集成服务门户(CCPortal): Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection

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DOI	10.1126/science.aba9301
	Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection
	Habibi M.S.; Thwaites R.S.; Chang M.; Jozwik A.; Paras A.; Kirsebom F.; Varese A.; Owen A.; Cuthbertson L.; James P.; Tunstall T.; Nickle D.; Hansel T.T.; Moffatt M.F.; Johansson C.; Chiu C.; Openshaw P.J.M.
发表日期	2020
ISSN	0036-8075
卷号	370 期号:6513
英文摘要	The variable outcome of viral exposure is only partially explained by known factors. We administered respiratory syncytial virus (RSV) to 58 volunteers, of whom 57% became infected. Mucosal neutrophil activation before exposure was highly predictive of symptomatic RSV disease. This was associated with a rapid, presymptomatic decline in mucosal interleukin-17A (IL-17A) and other mediators. Conversely, those who resisted infection showed presymptomatic activation of IL-17– and tumor necrosis factor–related pathways. Vulnerability to infection was not associated with baseline microbiome but was reproduced in mice by preinfection chemokine-driven airway recruitment of neutrophils, which caused enhanced disease mediated by pulmonary CD8+ T cell infiltration. Thus, mucosal neutrophilic inflammation at the time of RSV exposure enhances susceptibility, revealing dynamic, time-dependent local immune responses before symptom onset and explaining the as-yet unpredictable outcomes of pathogen exposure. © 2020 American Association for the Advancement of Science. All rights reserved.
英文关键词	chemokine; interleukin 17; tumor necrosis factor; CXCL1 chemokine; interleukin 17; tumor necrosis factor; cell component; cell organelle; factor analysis; immune response; respiratory disease; symptom; viral disease; adult; animal cell; animal experiment; animal model; animal tissue; Article; CD8+ T lymphocyte; controlled study; disease course; enzyme activation; female; human; human cell; human tissue; immune response; infection sensitivity; inflammation; leukocyte activation; lymphocytic infiltration; microflora; mouse; neutrophil; nonhuman; predictive value; priority journal; respiratory mucosa; respiratory syncytial virus infection; signal transduction; virus virulence; volunteer; adolescent; animal; C57BL mouse; CD4 lymphocyte count; CD4+ T lymphocyte; drug effect; immunology; inflammation; leukocyte activation; middle aged; neutrophil; nose mucosa; pathology; Pneumovirus; respiratory syncytial virus infection; virology; young adult; Respiratory syncytial virus; Adolescent; Adult; Animals; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Chemokine CXCL1; Humans; Inflammation; Interleukin-17; Mice; Mice, Inbred C57BL; Middle Aged; Nasal Mucosa; Neutrophil Activation; Neutrophils; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Tumor Necrosis Factor-alpha; Young Adult
语种	英语
来源期刊	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/243907
作者单位	National Heart and Lung Institute, Imperial College London, London, United Kingdom; Merck & Co., Inc., Kenilworth, NJ, United States; Genetics & Pharmacogenomics, Department of Translational Medicine, Merck & Co., Inc., Boston, MA, United States; Department of Infectious Disease, Imperial College London, London, United Kingdom
推荐引用方式 GB/T 7714	Habibi M.S.,Thwaites R.S.,Chang M.,et al. Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection[J],2020,370(6513).
APA	Habibi M.S..,Thwaites R.S..,Chang M..,Jozwik A..,Paras A..,...&Openshaw P.J.M..(2020).Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection.Science,370(6513).
MLA	Habibi M.S.,et al."Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection".Science 370.6513(2020).