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Corticosteroid suppression of antiviral immunity increases bacterial loads and mucus production in COPD exacerbations.
Singanayagam, Aran; Glanville, Nicholas; Girkin, Jason L; Ching, Yee Man; Marcellini, Andrea; Porter, James D; Toussaint, Marie; Walton, Ross P; Finney, Lydia J; Aniscenko, Julia; Zhu, Jie; Trujillo-Torralbo, Maria-Belen; Calderazzo, Maria Adelaide; Grainge, Chris; Loo, Su-Ling; Veerati, Punnam Chander; Pathinayake, Prabuddha S; Nichol, Kristy S; Reid, Andrew T; James, Phillip L; Solari, Roberto; Wark, Peter A B; Knight, Darryl A; Moffatt, Miriam F; Cookson, William O; Edwards, Michael R; Mallia, Patrick; Bartlett, Nathan W; Johnston, Sebastian L.
Afiliación
  • Singanayagam A; COPD and Asthma Section, National Heart and Lung Institute, Imperial College London, Norfolk Place, London, W2 1PG, UK.
  • Glanville N; COPD and Asthma Section, National Heart and Lung Institute, Imperial College London, Norfolk Place, London, W2 1PG, UK.
  • Girkin JL; Faculty of Health and Medicine and Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and University of Newcastle, Newcastle, NSW, 2305, Australia.
  • Ching YM; COPD and Asthma Section, National Heart and Lung Institute, Imperial College London, Norfolk Place, London, W2 1PG, UK.
  • Marcellini A; COPD and Asthma Section, National Heart and Lung Institute, Imperial College London, Norfolk Place, London, W2 1PG, UK.
  • Porter JD; COPD and Asthma Section, National Heart and Lung Institute, Imperial College London, Norfolk Place, London, W2 1PG, UK.
  • Toussaint M; COPD and Asthma Section, National Heart and Lung Institute, Imperial College London, Norfolk Place, London, W2 1PG, UK.
  • Walton RP; COPD and Asthma Section, National Heart and Lung Institute, Imperial College London, Norfolk Place, London, W2 1PG, UK.
  • Finney LJ; COPD and Asthma Section, National Heart and Lung Institute, Imperial College London, Norfolk Place, London, W2 1PG, UK.
  • Aniscenko J; COPD and Asthma Section, National Heart and Lung Institute, Imperial College London, Norfolk Place, London, W2 1PG, UK.
  • Zhu J; COPD and Asthma Section, National Heart and Lung Institute, Imperial College London, Norfolk Place, London, W2 1PG, UK.
  • Trujillo-Torralbo MB; COPD and Asthma Section, National Heart and Lung Institute, Imperial College London, Norfolk Place, London, W2 1PG, UK.
  • Calderazzo MA; COPD and Asthma Section, National Heart and Lung Institute, Imperial College London, Norfolk Place, London, W2 1PG, UK.
  • Grainge C; Faculty of Health and Medicine and Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and University of Newcastle, Newcastle, NSW, 2305, Australia.
  • Loo SL; Faculty of Health and Medicine and Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and University of Newcastle, Newcastle, NSW, 2305, Australia.
  • Veerati PC; Faculty of Health and Medicine and Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and University of Newcastle, Newcastle, NSW, 2305, Australia.
  • Pathinayake PS; Faculty of Health and Medicine and Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and University of Newcastle, Newcastle, NSW, 2305, Australia.
  • Nichol KS; Faculty of Health and Medicine and Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and University of Newcastle, Newcastle, NSW, 2305, Australia.
  • Reid AT; Faculty of Health and Medicine and Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and University of Newcastle, Newcastle, NSW, 2305, Australia.
  • James PL; Genomic Medicine, National Heart and Lung Institute, Imperial College London, Cale Street, London, SW3 6LY, UK.
  • Solari R; COPD and Asthma Section, National Heart and Lung Institute, Imperial College London, Norfolk Place, London, W2 1PG, UK.
  • Wark PAB; Faculty of Health and Medicine and Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and University of Newcastle, Newcastle, NSW, 2305, Australia.
  • Knight DA; Faculty of Health and Medicine and Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and University of Newcastle, Newcastle, NSW, 2305, Australia.
  • Moffatt MF; Genomic Medicine, National Heart and Lung Institute, Imperial College London, Cale Street, London, SW3 6LY, UK.
  • Cookson WO; Genomic Medicine, National Heart and Lung Institute, Imperial College London, Cale Street, London, SW3 6LY, UK.
  • Edwards MR; COPD and Asthma Section, National Heart and Lung Institute, Imperial College London, Norfolk Place, London, W2 1PG, UK.
  • Mallia P; COPD and Asthma Section, National Heart and Lung Institute, Imperial College London, Norfolk Place, London, W2 1PG, UK.
  • Bartlett NW; COPD and Asthma Section, National Heart and Lung Institute, Imperial College London, Norfolk Place, London, W2 1PG, UK. nathan.bartlett@newcastle.edu.au.
  • Johnston SL; Faculty of Health and Medicine and Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and University of Newcastle, Newcastle, NSW, 2305, Australia. nathan.bartlett@newcastle.edu.au.
Nat Commun ; 9(1): 2229, 2018 06 08.
Article en En | MEDLINE | ID: mdl-29884817
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-ß 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/ß 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-ß therapy may protect.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Rhinovirus / Corticoesteroides / Enfermedad Pulmonar Obstructiva Crónica / Carga Bacteriana / Inmunidad Innata / Moco Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2018 Tipo del documento: Article País de afiliación: Reino Unido
Texto completo
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XML
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Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Rhinovirus / Corticoesteroides / Enfermedad Pulmonar Obstructiva Crónica / Carga Bacteriana / Inmunidad Innata / Moco Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2018 Tipo del documento: Article País de afiliación: Reino Unido