Impaired innate interferon induction in severe therapy resistant atopic asthmatic children
Open accessAbstract
Deficient type I interferon-β and type III interferon-λ induction by rhinoviruses has previously been reported in mild/moderate atopic asthmatic adults. No studies have yet investigated if this occurs in severe therapy resistant asthma (STRA). Here, we show that compared with non-allergic healthy control children, bronchial epithelial cells cultured ex vivo from severe therapy resistant atopic asthmatic children have profoundly impaired interferon-β and interferon-λ mRNA and protein in response to rhinovirus (RV) and polyIC stimulation. Severe treatment resistant asthmatics also exhibited increased virus load, which negatively correlated with interferon mRNA levels. Furthermore, uninfected cells from severe therapy resistant asthmatic children showed lower levels of Toll-like receptor-3 mRNA and reduced retinoic acid inducible gene and melanoma differentiation-associated gene 5 mRNA after RV stimulation. These data expand on the original work, suggesting that the innate anti-viral response to RVs is impaired in asthmatic tissues and demonstrate that this is a feature of STRA.
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Impaired innate anti-viral immunity with diminished interferon induction to rhinovirus has been reported in both children and adults with severe asthma.
“Impaired innate anti-viral immunity with diminished interferon induction to rhinovirus has been reported in both children and adults with severe asthma (77–79).”
From Epidemiology of Asthma in Children and Adults (2019) · cites this paper as [79]
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Self-citation
- Authors
- Edwards, M. R., Regamey, N., Vareille, M., Kieninger, E., Gupta, A., Shoemark, A., Saglani, S., Sykes, A., Macintyre, J., Davies, J., Bossley, C., Bush, A., & Johnston, S. L.
- Affiliations
- Asthma UK (GB)
- University of Bern (CH)
- Royal Brompton Hospital (GB)
- Corresponding author
- Edwards, M R
- ORCID
- Venue
- Mucosal Immunology
- Publisher
- Elsevier BV
- Published
- 2013-07
- Volume
- 6
- Issue
- 4
- Pages
- 797-806
- ISSN
- 1933-0219 (ISSN-L)
- PMC
- PMC3684776
- OpenAlex
- W2141157966
- Cited by
- 214
- References
- 47
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 8 · 2023: 13 · 2022: 12 · 2021: 18 · 2020: 23 · 2019: 25 · 2018: 14 · 2017: 18 · 2016: 22 · 2015: 24 · 2014: 17 · 2013: 8
- FWCI
- 6.85
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Mucosal Immunology (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion, cc-by-nc-nd)
- Bern Open Repository and Information System (University of Bern) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion, cc-by-nc-nd)
- Funders
- Wellcome Trust (083567/Z/07/Z)
- Royal Brompton and Harefield NHS Foundation Trust
- National Institute for Health and Care Research (NF-SI-0508-10212, NF-SI-0510-10192)
- British Lung Foundation
- Asthma and Lung UK (G1000758, CH11SJ)
- Imperial College London
- European Commission (260895)
- Medical Research Council (G1000758)
- FP7 Ideas: European Research Council (233015)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Keywords
- allergic asthma, children, type I interferon, interferon-beta, interferon lambda, rhinovirus, antiviral innate immunity, bronchial epithelial cells, poly(I:C), TLR3, RIG-I, MDA5, viral load, viral infection
- MeSH terms
- DEAD Box Protein 58, Interferon-Induced Helicase, IFIH1, Adolescent, Asthma, Child, Child, Preschool, Female, Gene Expression Regulation, Humans, Hypersensitivity, Immediate, Immunoglobulin E, Immunity, Innate, Interferon-gamma, Interferons, Lung, Male, Picornaviridae Infections, Poly I-C, Receptors, Immunologic, Rhinovirus, RNA, Messenger, Time Factors, Interleukin-8, Interferon-beta, Respiratory Mucosa, Toll-Like Receptor 3, DEAD-box RNA Helicases
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