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Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection

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Maximillian S. Habibi, Ryan S. Thwaites, Meiping Chang, Agnieszka Jozwik, Allan Paras, Freja Kirsebom, Augusto Varese, Amber Owen, Leah Cuthbertson, Phillip James, Tanushree Tunstall, David Nickle, Trevor T. Hansel, Miriam F. Moffatt, Cecilia Johansson, Christopher Chiu, Peter J. M. Openshaw

Original languageEnglish
Article numbereaba9301
Pages (from-to)eaba9301
JournalScience
Volume370
Issue number6513
DOIs
Accepted/In press9 Oct 2020
Published9 Oct 2020

King's Authors

Abstract

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.

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