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Antiviral immunity is impaired in COPD patients with frequent exacerbations.
Singanayagam, Aran; Loo, Su-Ling; Calderazzo, Maria; Finney, Lydia J; Trujillo Torralbo, Maria-Belen; Bakhsoliani, Eteri; Girkin, Jason; Veerati, Punnam; Pathinayake, Prabuddha S; Nichol, Kristy S; Reid, Andrew; Footitt, Joseph; Wark, Peter A B; Grainge, Christopher L; Johnston, Sebastian L; Bartlett, Nathan W; Mallia, Patrick.
Afiliación
  • Singanayagam A; National Heart and Lung Institute, Imperial College London, London, United Kingdom.
  • Loo SL; Faculty of Health and Medicine and Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and University of Newcastle, Newcastle, New South Wales, Australia.
  • Calderazzo M; National Heart and Lung Institute, Imperial College London, London, United Kingdom.
  • Finney LJ; National Heart and Lung Institute, Imperial College London, London, United Kingdom.
  • Trujillo Torralbo MB; National Heart and Lung Institute, Imperial College London, London, United Kingdom.
  • Bakhsoliani E; National Heart and Lung Institute, Imperial College London, London, United Kingdom.
  • Girkin J; Faculty of Health and Medicine and Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and University of Newcastle, Newcastle, New South Wales, Australia.
  • Veerati P; Faculty of Health and Medicine and Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and University of Newcastle, Newcastle, New South Wales, Australia.
  • Pathinayake PS; Faculty of Health and Medicine and Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and University of Newcastle, Newcastle, New South Wales, Australia.
  • Nichol KS; Faculty of Health and Medicine and Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and University of Newcastle, Newcastle, New South Wales, Australia.
  • Reid A; Faculty of Health and Medicine and Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and University of Newcastle, Newcastle, New South Wales, Australia.
  • Footitt J; National Heart and Lung Institute, Imperial College London, London, United Kingdom.
  • Wark PAB; National Heart and Lung Institute, Imperial College London, London, United Kingdom.
  • Grainge CL; Faculty of Health and Medicine and Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and University of Newcastle, Newcastle, New South Wales, Australia.
  • Johnston SL; National Heart and Lung Institute, Imperial College London, London, United Kingdom.
  • Bartlett NW; National Heart and Lung Institute, Imperial College London, London, United Kingdom.
  • Mallia P; Faculty of Health and Medicine and Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and University of Newcastle, Newcastle, New South Wales, Australia.
Am J Physiol Lung Cell Mol Physiol ; 317(6): L893-L903, 2019 12 01.
Article en En | MEDLINE | ID: mdl-31513433
Patients with frequent exacerbations represent a chronic obstructive pulmonary disease (COPD) subgroup requiring better treatment options. The aim of this study was to determine the innate immune mechanisms that underlie susceptibility to frequent exacerbations in COPD. We measured sputum expression of immune mediators and bacterial loads in samples from patients with COPD at stable state and during virus-associated exacerbations. In vitro immune responses to rhinovirus infection in differentiated primary bronchial epithelial cells (BECs) sampled from patients with COPD were additionally evaluated. Patients were stratified as frequent exacerbators (≥2 exacerbations in the preceding year) or infrequent exacerbators (<2 exacerbations in the preceding year) with comparisons made between these groups. Frequent exacerbators had reduced sputum cell mRNA expression of the antiviral immune mediators type I and III interferons and reduced interferon-stimulated gene (ISG) expression when clinically stable and during virus-associated exacerbation. A role for epithelial cell-intrinsic innate immune dysregulation was identified: induction of interferons and ISGs during in vitro rhinovirus (RV) infection was also impaired in differentiated BECs from frequent exacerbators. Frequent exacerbators additionally had increased sputum bacterial loads at 2 wk following virus-associated exacerbation onset. These data implicate deficient airway innate immunity involving epithelial cells in the increased propensity to exacerbations observed in some patients with COPD. Therapeutic approaches to boost innate antimicrobial immunity in the lung could be a viable strategy for prevention and treatment of frequent exacerbations.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Insuficiencia Respiratoria / Rhinovirus / Esputo / Bronquios / Infecciones por Picornaviridae / Enfermedad Pulmonar Obstructiva Crónica / Inmunidad Innata Tipo de estudio: Observational_studies / Risk_factors_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Am J Physiol Lung Cell Mol Physiol Asunto de la revista: BIOLOGIA MOLECULAR / FISIOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Estados Unidos
Texto completo
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Insuficiencia Respiratoria / Rhinovirus / Esputo / Bronquios / Infecciones por Picornaviridae / Enfermedad Pulmonar Obstructiva Crónica / Inmunidad Innata Tipo de estudio: Observational_studies / Risk_factors_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Am J Physiol Lung Cell Mol Physiol Asunto de la revista: BIOLOGIA MOLECULAR / FISIOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Estados Unidos