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Obesity dysregulates the pulmonary antiviral immune response

Author

Listed:
  • Mark Almond

    (Imperial College London)

  • Hugo A. Farne

    (Imperial College London)

  • Millie M. Jackson

    (Imperial College London)

  • Akhilesh Jha

    (University of Cambridge)

  • Orestis Katsoulis

    (Imperial College London)

  • Oliver Pitts

    (Imperial College London)

  • Tanushree Tunstall

    (Imperial College London)

  • Eteri Regis

    (Imperial College London)

  • Jake Dunning

    (University of Oxford)

  • Adam J. Byrne

    (Imperial College London
    University College Dublin)

  • Patrick Mallia

    (Imperial College London)

  • Onn Min Kon

    (Imperial College London)

  • Ken A. Saunders

    (GSK)

  • Karen D. Simpson

    (GSK)

  • Robert J. Snelgrove

    (Imperial College London)

  • Peter J. M. Openshaw

    (Imperial College London)

  • Michael R. Edwards

    (Imperial College London)

  • Wendy S. Barclay

    (Imperial College London)

  • Liam M. Heaney

    (Loughborough University)

  • Sebastian L. Johnston

    (Imperial College London)

  • Aran Singanayagam

    (Imperial College London)

Abstract

Obesity is a well-recognized risk factor for severe influenza infections but the mechanisms underlying susceptibility are poorly understood. Here, we identify that obese individuals have deficient pulmonary antiviral immune responses in bronchoalveolar lavage cells but not in bronchial epithelial cells or peripheral blood dendritic cells. We show that the obese human airway metabolome is perturbed with associated increases in the airway concentrations of the adipokine leptin which correlated negatively with the magnitude of ex vivo antiviral responses. Exogenous pulmonary leptin administration in mice directly impaired antiviral type I interferon responses in vivo and ex vivo in cultured airway macrophages. Obese individuals hospitalised with influenza showed dysregulated upper airway immune responses. These studies provide insight into mechanisms driving propensity to severe influenza infections in obesity and raise the potential for development of leptin manipulation or interferon administration as novel strategies for conferring protection from severe infections in obese higher risk individuals.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42432-x
    DOI: 10.1038/s41467-023-42432-x
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    References listed on IDEAS

    as
    1. 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.
    2. Yasuhiko Minokoshi & Young-Bum Kim & Odile D. Peroni & Lee G. D. Fryer & Corinna Müller & David Carling & Barbara B. Kahn, 2002. "Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase," Nature, Nature, vol. 415(6869), pages 339-343, January.
    Full references (including those not matched with items on IDEAS)

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