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J Allergy Clin Immunol. 2019 Jan;143(1):114-125.e4. doi: 10.1016/j.jaci.2018.04.003. Epub 2018 Apr 24.

Bronchial mucosal IFN-α/β and pattern recognition receptor expression in patients with experimental rhinovirus-induced asthma exacerbations.

Author information

1
Airway Disease Infection, National Heart and Lung Institute, Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma, Imperial College London, London, United Kingdom.
2
Airway Disease Infection, National Heart and Lung Institute, Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma, Imperial College London, London, United Kingdom; Imperial College Healthcare NHS Trust, London, United Kingdom.
3
Airway Disease Infection, National Heart and Lung Institute, Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma, Imperial College London, London, United Kingdom; Imperial College Healthcare NHS Trust, London, United Kingdom; Research Centre on Asthma and COPD, University of Ferrara, Ferrara, Italy.
4
Centocor, Malvern, Pa.
5
Imperial College Healthcare NHS Trust, London, United Kingdom.
6
Research Centre on Asthma and COPD, University of Ferrara, Ferrara, Italy.
7
Airway Disease Infection, National Heart and Lung Institute, Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma, Imperial College London, London, United Kingdom; Imperial College Healthcare NHS Trust, London, United Kingdom. Electronic address: s.johnston@imperial.ac.uk.

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.

KEYWORDS:

Asthma exacerbation; pattern recognition receptors; rhinovirus infection; type I interferon

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