Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection

Author:

Habibi Maximillian S.1ORCID,Thwaites Ryan S.1ORCID,Chang Meiping2,Jozwik Agnieszka1,Paras Allan1ORCID,Kirsebom Freja1ORCID,Varese Augusto1,Owen Amber1ORCID,Cuthbertson Leah1ORCID,James Phillip1,Tunstall Tanushree1,Nickle David3,Hansel Trevor T.1ORCID,Moffatt Miriam F.1ORCID,Johansson Cecilia1ORCID,Chiu Christopher4ORCID,Openshaw Peter J. M.1ORCID

Affiliation:

1. National Heart and Lung Institute, Imperial College London, London, UK.

2. Merck & Co., Inc., Kenilworth, NJ, USA.

3. Genetics & Pharmacogenomics, Department of Translational Medicine, Merck & Co., Inc., Boston, MA, USA.

4. Department of Infectious Disease, Imperial College London, London, UK.

Abstract

ACHOO!-trophils? Why some individuals come down with a cold in any given year, whereas others are spared, is poorly understood. Habibi et al. exposed volunteers to respiratory syncytial virus (RSV), one of the pathogens responsible for the common cold, and then followed them over the ensuing 2 weeks (see the Perspective by Mirchandani and Walmsley). The main factor distinguishing the infected from the noninfected was that the former showed signs of airway neutrophil activation before exposure to RSV. Conversely, protected individuals showed enhanced interleukin-17 signaling soon after virus inoculation. Similarly, mice pretreated with a neutrophil chemoattractant were more susceptible to RSV infection and CD8 + T cell–driven disease. Neutrophil proteases, which can modulate cytokine activity, may explain the disparity and could provide therapeutic targets for RSV and other respiratory infections. Science , this issue p. eaba9301 ; see also p. 166

Funder

Wellcome

Horizon 2020 Framework Programme

Medical Research Council

NIHR Imperial Biomedical Research Centre

NIHR Health Protection Research Unit in Respiratory Infections

NIHR Comprehensive Local Research Networks

European Respiratory Society and the Asociación Latinoamericana de Tórax joint long- term Research Fellowship 2019

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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