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Corticosteroid suppression of antiviral immunity increases bacterial loads and mucus production in COPD exacerbations

Author

Listed:
  • Aran Singanayagam

    (Imperial College London)

  • Nicholas Glanville

    (Imperial College London)

  • Jason L. Girkin

    (Hunter Medical Research Institute and University of Newcastle)

  • Yee Man Ching

    (Imperial College London)

  • Andrea Marcellini

    (Imperial College London)

  • James D. Porter

    (Imperial College London)

  • Marie Toussaint

    (Imperial College London)

  • Ross P. Walton

    (Imperial College London)

  • Lydia J. Finney

    (Imperial College London)

  • Julia Aniscenko

    (Imperial College London)

  • Jie Zhu

    (Imperial College London)

  • Maria-Belen Trujillo-Torralbo

    (Imperial College London)

  • Maria Adelaide Calderazzo

    (Imperial College London)

  • Chris Grainge

    (Hunter Medical Research Institute and University of Newcastle)

  • Su-Ling Loo

    (Hunter Medical Research Institute and University of Newcastle)

  • Punnam Chander Veerati

    (Hunter Medical Research Institute and University of Newcastle)

  • Prabuddha S. Pathinayake

    (Hunter Medical Research Institute and University of Newcastle)

  • Kristy S. Nichol

    (Hunter Medical Research Institute and University of Newcastle)

  • Andrew T. Reid

    (Hunter Medical Research Institute and University of Newcastle)

  • Phillip L. James

    (Imperial College London)

  • Roberto Solari

    (Imperial College London)

  • Peter A. B. Wark

    (Hunter Medical Research Institute and University of Newcastle)

  • Darryl A. Knight

    (Hunter Medical Research Institute and University of Newcastle)

  • Miriam F. Moffatt

    (Imperial College London)

  • William O. Cookson

    (Imperial College London)

  • Michael R. Edwards

    (Imperial College London)

  • Patrick Mallia

    (Imperial College London)

  • Nathan W. Bartlett

    (Imperial College London
    Hunter Medical Research Institute and University of Newcastle)

  • Sebastian L. Johnston

    (Imperial College London)

Abstract

Inhaled corticosteroids (ICS) have limited efficacy in reducing chronic obstructive pulmonary disease (COPD) exacerbations and increase pneumonia risk, through unknown mechanisms. Rhinoviruses precipitate most exacerbations and increase susceptibility to secondary bacterial infections. Here, we show that the ICS fluticasone propionate (FP) impairs innate and acquired antiviral immune responses leading to delayed virus clearance and previously unrecognised adverse effects of enhanced mucus, impaired antimicrobial peptide secretion and increased pulmonary bacterial load during virus-induced exacerbations. Exogenous interferon-β reverses these effects. FP suppression of interferon may occur through inhibition of TLR3- and RIG-I virus-sensing pathways. Mice deficient in the type I interferon-α/β receptor (IFNAR1−/−) have suppressed antimicrobial peptide and enhanced mucin responses to rhinovirus infection. This study identifies type I interferon as a central regulator of antibacterial immunity and mucus production. Suppression of interferon by ICS during virus-induced COPD exacerbations likely mediates pneumonia risk and raises suggestion that inhaled interferon-β therapy may protect.

Suggested Citation

  • Aran Singanayagam & Nicholas Glanville & Jason L. Girkin & Yee Man Ching & Andrea Marcellini & James D. Porter & Marie Toussaint & Ross P. Walton & Lydia J. Finney & Julia Aniscenko & Jie Zhu & Maria-, 2018. "Corticosteroid suppression of antiviral immunity increases bacterial loads and mucus production in COPD exacerbations," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04574-1
    DOI: 10.1038/s41467-018-04574-1
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    Cited by:

    1. Haibo Zhang & Keke Xue & Wen Li & Xinyi Yang & Yusen Gou & Xiao Su & Feng Qian & Lei Sun, 2024. "Cullin5 drives experimental asthma exacerbations by modulating alveolar macrophage antiviral immunity," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Mark Almond & Hugo A. Farne & Millie M. Jackson & Akhilesh Jha & Orestis Katsoulis & Oliver Pitts & Tanushree Tunstall & Eteri Regis & Jake Dunning & Adam J. Byrne & Patrick Mallia & Onn Min Kon & Ken, 2023. "Obesity dysregulates the pulmonary antiviral immune response," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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