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Bronchial mucosal IFN-α/β and pattern recognition receptor expression in patients with experimental rhinovirus-induced asthma exacerbations.
J Allergy Clin Immunol 2019; 143(1):114-125.e4JA

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.

Authors+Show Affiliations

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.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.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.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.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.Centocor, Malvern, Pa.Centocor, Malvern, Pa.Centocor, Malvern, Pa.Imperial College Healthcare NHS Trust, London, United Kingdom.Research Centre on Asthma and COPD, University of Ferrara, Ferrara, Italy.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.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.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.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.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29698627

Citation

Zhu, Jie, et al. "Bronchial Mucosal IFN-α/β and Pattern Recognition Receptor Expression in Patients With Experimental Rhinovirus-induced Asthma Exacerbations." The Journal of Allergy and Clinical Immunology, vol. 143, no. 1, 2019, pp. 114-125.e4.
Zhu J, Message SD, Mallia P, et al. Bronchial mucosal IFN-α/β and pattern recognition receptor expression in patients with experimental rhinovirus-induced asthma exacerbations. J Allergy Clin Immunol. 2019;143(1):114-125.e4.
Zhu, J., Message, S. D., Mallia, P., Kebadze, T., Contoli, M., Ward, C. K., ... Johnston, S. L. (2019). Bronchial mucosal IFN-α/β and pattern recognition receptor expression in patients with experimental rhinovirus-induced asthma exacerbations. The Journal of Allergy and Clinical Immunology, 143(1), pp. 114-125.e4. doi:10.1016/j.jaci.2018.04.003.
Zhu J, et al. Bronchial Mucosal IFN-α/β and Pattern Recognition Receptor Expression in Patients With Experimental Rhinovirus-induced Asthma Exacerbations. J Allergy Clin Immunol. 2019;143(1):114-125.e4. PubMed PMID: 29698627.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bronchial mucosal IFN-α/β and pattern recognition receptor expression in patients with experimental rhinovirus-induced asthma exacerbations. AU - Zhu,Jie, AU - Message,Simon D, AU - Mallia,Patrick, AU - Kebadze,Tatiana, AU - Contoli,Marco, AU - Ward,Christine K, AU - Barnathan,Elliot S, AU - Mascelli,Mary Ann, AU - Kon,Onn M, AU - Papi,Alberto, AU - Stanciu,Luminita A, AU - Edwards,Michael R, AU - Jeffery,Peter K, AU - Johnston,Sebastian L, Y1 - 2018/04/24/ PY - 2017/08/25/received PY - 2018/03/12/revised PY - 2018/04/03/accepted PY - 2018/4/27/pubmed PY - 2018/4/27/medline PY - 2018/4/27/entrez KW - Asthma exacerbation KW - pattern recognition receptors KW - rhinovirus infection KW - type I interferon SP - 114 EP - 125.e4 JF - The Journal of allergy and clinical immunology JO - J. Allergy Clin. Immunol. VL - 143 IS - 1 N2 - 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. SN - 1097-6825 UR - https://www.unboundmedicine.com/medline/citation/29698627/Bronchial_mucosal_IFN_α/β_and_pattern_recognition_receptor_expression_in_patients_with_experimental_rhinovirus_induced_asthma_exacerbations_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-6749(18)30610-9 DB - PRIME DP - Unbound Medicine ER -