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  • In vivo bronchial epithelial interferon responses are augmented in asthma on day 4 following experimental rhinovirus infection

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In vivo bronchial epithelial interferon responses are augmented in asthma on day 4 following experimental rhinovirus infection
  1. Hugo Farne1,
  2. Lijing Lin2,
  3. David J Jackson1,3,4,
  4. Magnus Rattray2,
  5. Angela Simpson5,
  6. Adnan Custovic6,
  7. Shilpy Joshi7,
  8. Paul A Wilson7,
  9. Rick Williamson7,
  10. Michael R Edwards1,
  11. Aran Singanayagam8,
  12. Sebastian L Johnston1
  1. 1 National Heart and Lung Institute, Imperial College London, London, UK
  2. 2 Division of Informatics, Imaging & Data Sciences, The University of Manchester, Manchester, UK
  3. 3 Guy's Severe Asthma Centre, Guy's and St Thomas' NHS Foundation Trust, London, UK
  4. 4 MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, London, UK
  5. 5 Division of Infection, Immunity & Respiratory Medicine, The University of Manchester, Manchester, UK
  6. 6 Department of Paediatrics, Imperial College London, London, UK
  7. 7 GlaxoSmithKline Plc, Brentford, UK
  8. 8 Department of Infectious Disease, Imperial College, London, UK
  1. Correspondence to Professor Sebastian L Johnston, Imperial College London, London SW7 2AZ, UK; s.johnston{at}imperial.ac.uk

Abstract

Despite good evidence of impaired innate antiviral responses in asthma, trials of inhaled interferon-β given during exacerbations showed only modest benefits in moderate/severe asthma. Using human experimental rhinovirus infection, we observe robust in vivo induction of bronchial epithelial interferon response genes 4 days after virus inoculation in 25 subjects with asthma but not 11 control subjects. This signature correlated with virus loads and lower respiratory symptoms. Our data indicate that the in vivo innate antiviral response is dysregulated in asthma and open up the potential that prophylactic rather than therapeutic interferon therapy may have greater clinical benefit.

  • Asthma
  • Asthma Mechanisms
  • Innate Immunity
  • Viral infection

http://dx.doi.org/10.1136/thoraxjnl-2021-217389

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    Footnotes

    • HF, LL and DJJ are joint first authors.

    • Twitter @drhugoa, @SinganayagamLab

    • HF, LL and DJJ contributed equally.

    • Contributors All authors contributed to data interpretation and the writing and reviewing of the manuscript, took responsibility for the integrity of the complete work and gave final approval for the version to be published. DJJ, MR and SJ conceived and designed the clinical study, subsequently led by DJJ including the collection of clinical data and samples used in this analysis. SJ, PAW and RW performed the transcriptomic experiments. HF, LL, MR, AnS, AC and ArS conceived the transcriptomic analysis, carried out by HF and LL independently. All authors interpreted the data. HF prepared the manuscript, which was critically revised for important intellectual content by ArS and SLJ. All authors read and approved the final version.

    • Funding This study was supported by the European Research Council (ERC FP7 grant 233015), MRC grant MR/L012693/1, MRC Centre grant G1000758, National Institute of Healthcare Research Imperial Biomedical Research Centre (NIHR BRC) grant P26095, Predicta FP7 Collaborative Project grant 260 895 by the NIHR BRC at Imperial College London. HF is supported by the NIHR Clinical Lecturer funding scheme. SLJ is an NIHR Emeritus Senior Investigator, the Asthma UK Clinical Chair (Grant CH11SJ) and receives support from European Research Council Advanced Grant 788 575 and Asthma UK Centre Grant AUK-BC-2015-01.

    • Disclaimer The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The Funders did not have a role in study design, data collection, data analysis, interpretation, and writing of the report.

    • Competing interests HF and LL report no competing interests. DJJ reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, and Novartis outside the submitted work. MR and AnS report personal fees from AstraZeneca outside the submitted work. AC reports personal fees from Novartis, Thermo Fisher Scientific, Philips, Sanofi, Stallergenes Greer, and AstraZeneca outside the submitted work. SJ, PAW and RW are GlaxoSmithKline employees. MRE is a Virtus Respiratory Research employee. SLJ personal fees from Virtus Respiratory Research, Myelo Therapeutics, Bayer, Synairgen, Novartis, Boehringer Ingelheim, Chiesi, Gerson Lehrman Group, resTORbio, Bioforce, Materia Medical Holdings, PrepBio Pharma, Pulmotect, Virion Health, Lallemand Pharma, and AstraZeneca outside the submitted work; in addition SLJ is an author on patents relating to use of interferons in treatment of exacerbations of airway disease.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.