Bronchial mucosal IFN-?/? and pattern recognition receptor expression in patients with experimental rhinovirus-induced asthma exacerbations - 04/01/19
Abstract |
Background |
The innate immune system senses viral infection through pattern recognition receptors (PRRs), leading to type I interferon production. The role of type I interferon and PPRs in rhinovirus-induced asthma exacerbations in vivo are uncertain.
Objectives |
We sought to compare bronchial mucosal type I interferon and PRR expression at baseline and after rhinovirus infection in atopic asthmatic patients and control subjects.
Methods |
Immunohistochemistry was used to detect expression of IFN-α, IFN-β, and the PRRs: Toll-like receptor 3, melanoma differentiation–associated gene 5, and retinoic acid–inducible protein I in bronchial biopsy specimens from 10 atopic asthmatic patients and 15 nonasthmatic nonatopic control subjects at baseline and on day 4 and 6 weeks after rhinovirus infection.
Results |
We observed IFN-α/β deficiency in the bronchial epithelium at 3 time points in asthmatic patients in vivo. Lower epithelial IFN-α/β expression was related to greater viral load, worse airway symptoms, airway hyperresponsiveness, and reductions in lung function during rhinovirus infection. We found lower frequencies of bronchial subepithelial monocytes/macrophages expressing IFN-α/β in asthmatic patients during infection. Interferon deficiency at baseline was not accompanied by deficient PRR expression in asthmatic patients. Both epithelial and subepithelial PRR expression were induced during rhinovirus infection. Rhinovirus infection–increased numbers of subepithelial interferon/PRR-expressing inflammatory cells were related to greater viral load, airway hyperresponsiveness, and reductions in lung function.
Conclusions |
Bronchial epithelial IFN-α/β expression and numbers of subepithelial IFN-α/β–expressing monocytes/macrophages during infection were both deficient in asthmatic patients. Lower epithelial IFN-α/β expression was associated with adverse clinical outcomes after rhinovirus infection in vivo. Increases in numbers of subepithelial cells expressing interferon/PRRs during infection were also related to greater viral load/illness severity.
Le texte complet de cet article est disponible en PDF.Key words : Asthma exacerbation, rhinovirus infection, type I interferon, pattern recognition receptors
Abbreviations used : AHR, BAL, HRP, MDA5, PEF, PRR, RIG-I, RV16, TLR
Plan
| Supported by a Medical Research Council (MRC) Clinical Research Fellowship and a British Medical Association HC Roscoe Fellowship (SDM), British Lung Foundation/Severin Wunderman Family Foundation Lung Research Programme grant no. P00/2, Asthma UK project grant nos. 02/027 and 05/067, the National Institute of Health Research (NIHR) Biomedical Research Centre and Clinical Lecturer funding schemes, Centocor, MRC Centre grant G1000758, and ERC FP7 Advanced grant 233015. S.L.J. is the Asthma UK Clinical Chair (grant CH11SJ) and is an NIHR Senior Investigator. |
|
| Disclosure of potential conflict of interest: M. Contoli reports grants from Chiesi, personal fees from Chiesi, AstraZeneca, Boehringer Ingelheim, Chiesi, AstraZeneca, Novartis, Menarini, Mundipharma, Almirall, and Zambon outside the submitted work. A. Papi reports grants, personal fees, nonfinancial support, and other support from Chiesi, AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, and Merck Sharp & Dohme; personal fees and nonfinancial support from Menarini, Novartis, and Zambon; and grants, personal fees, nonfinancial support, and other support from Pfizer, Takeda, Mundipharma, and Teva outside the submitted work. S. L. Johnston reports board membership for Therapeutic Frontiers; consultancy fees from Myelo Therapeutics GmbH, Concert Pharmaceuticals, Bayer, Synairgen, Novartis, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Sanofi Pasteur, Centocor, and Aviragen; money paid to his institution for consultancy fees by Synairgen, Novartis, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, and Centocor; and patents (International Patent Application No. PCT/GB05/50031, UK Patent Application No. 0518425.4, Patent No. 7569216, European Patent No. 1734987, Hong Kong Patent No. 1097181, Japanese Patent No. 4807526, New Hong Kong Divisional Patent Application No. 11100187.0, and European Patent No. 13305152). The rest of the authors declare that they have no relevant conflicts to disclose. |
Vol 143 - N° 1
P. 114 - janvier 2019 Retour au numéro
Article précédent
- Refractory airway type 2 inflammation in a large subgroup of asthmatic patients treated with inhaled corticosteroids
- Michael C. Peters, Sheena Kerr, Eleanor M. Dunican, Prescott G. Woodruff, Merritt L. Fajt, Bruce D. Levy, Elliot Israel, Brenda R. Phillips, David T. Mauger, Suzy A. Comhair, Serpil C. Erzurum, Mats W. Johansson, Nizar N. Jarjour, Andrea M. Coverstone, Mario Castro, Annette T. Hastie, Eugene R. Bleecker, Sally E. Wenzel, John V. Fahy, National Heart, Lung and Blood Institute Severe Asthma Research Program 3
- NAVIGATE II: Randomized, double-blind trial of the exhalation delivery system with fluticasone for nasal polyposis
- Donald A. Leopold, David Elkayam, John C. Messina, Colette Kosik-Gonzalez, Per G. Djupesland, Ramy A. Mahmoud
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?