Impaired innate interferon induction in severe therapy resistant atopic asthmatic children

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 (2013). Impaired innate interferon induction in severe therapy resistant atopic asthmatic children. Mucosal immunology, 6(4), pp. 797-806. New York, N.Y.: Nature Publishing Group 10.1038/mi.2012.118

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine

UniBE Contributor:

Regamey, Nicolas; Vareille, Marjolaine and Kieninger, Elisabeth

ISSN:

1933-0219

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:41

Last Modified:

17 Mar 2015 21:35

Publisher DOI:

10.1038/mi.2012.118

PubMed ID:

23212197

Web of Science ID:

000322535800013

URI:

https://boris.unibe.ch/id/eprint/16538 (FactScience: 224193)

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