Role of deficient type III interferon-λ production in asthma exacerbations
Abstract
Rhinoviruses are the major cause of asthma exacerbations, and asthmatics have increased susceptibility to rhinovirus and risk of invasive bacterial infections. Here we show deficient induction of interferon-lambdas by rhinovirus in asthmatic primary bronchial epithelial cells and alveolar macrophages, which was highly correlated with severity of rhinovirus-induced asthma exacerbation and virus load in experimentally infected human volunteers. Induction by lipopolysaccharide in asthmatic macrophages was also deficient and correlated with exacerbation severity. These results identify previously unknown mechanisms of susceptibility to infection in asthma and suggest new approaches to prevention and/or treatment of asthma exacerbations.
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Abnormal repair processes of the airway epithelium leading to abnormal organization and integrity of the respiratory epithelium, with subsequent perturbations in innate immune functions, have been proposed as key mechanisms in the pathogenesis of chronic airway diseases such as asthma and COPD.
“Abnormal repair processes of the airway epithelium leading to abnormal organization and integrity of the respiratory epithelium, with subsequent perturbations in innate immune functions, have been proposed as key mechanisms in the pathogenesis of chronic airway diseases such as asthma (38, 48) and COPD (221).”
From The airway epithelium: soldier in the fight against respiratory viruses (2011) · cites this paper as [38]
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- Authors
- Contoli, M., Message, S. D., Laza-Stanca, V., Edwards, M. R., Wark, P. A. B., Bartlett, N. W., Kebadze, T., Mallia, P., Stanciu, L. A., Parker, H. L., Slater, L., Lewis-Antes, A., Kon, O. M., Holgate, S. T., Davies, D. E., Kotenko, S. V., Papi, A., & Johnston, S. L.
- Affiliations
- Asthma UK (GB)
- Southampton General Hospital (GB)
- Rutgers New Jersey Medical School (US)
- St Mary's Hospital (GB)
- University of Ferrara (IT)
- Corresponding author
- Johnston, Sebastian L
- ORCID
- Venue
- Nature Medicine
- Published
- 2006-08-13
- Volume
- 12
- Issue
- 9
- Pages
- 1023-1026
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2007736853
- Cited by
- 1,006
- References
- 14
- Citations by year
- 2026: 18 · 2025: 22 · 2024: 18 · 2023: 31 · 2022: 40 · 2021: 55 · 2020: 48 · 2019: 45 · 2018: 38 · 2017: 59 · 2016: 63 · 2015: 55 · 2014: 85 · 2013: 78 · 2012: 71
- FWCI
- 20.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (AI051139, R01AI057468, R01AI051139, AI057468)
- 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
- asthma exacerbations, interferon lambda, rhinovirus, bronchial epithelial cells, alveolar macrophages, infection susceptibility, lipopolysaccharide, viral load, invasive bacterial infection
- MeSH terms
- Interferon Lambda, Asthma, Bronchoalveolar Lavage Fluid, Cells, Cultured, Humans, Interferons, Interleukins, Lipopolysaccharides, Picornaviridae Infections, Rhinovirus, Cytokines
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