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Impaired innate interferon induction in severe therapy resistant atopic asthmatic children.
Mucosal Immunol 2013; 6(4):797-806MI

Abstract

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.

Authors+Show Affiliations

Respiratory Medicine, St Mary's Campus, National Heart Lung Institute, London, UK. michael.edwards@imperial.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23212197

Citation

Edwards, M R., et al. "Impaired Innate Interferon Induction in Severe Therapy Resistant Atopic Asthmatic Children." Mucosal Immunology, vol. 6, no. 4, 2013, pp. 797-806.
Edwards MR, Regamey N, Vareille M, et al. Impaired innate interferon induction in severe therapy resistant atopic asthmatic children. Mucosal Immunol. 2013;6(4):797-806.
Edwards, M. R., Regamey, N., Vareille, M., Kieninger, E., Gupta, A., Shoemark, A., ... Johnston, S. L. (2013). Impaired innate interferon induction in severe therapy resistant atopic asthmatic children. Mucosal Immunology, 6(4), pp. 797-806. doi:10.1038/mi.2012.118.
Edwards MR, et al. Impaired Innate Interferon Induction in Severe Therapy Resistant Atopic Asthmatic Children. Mucosal Immunol. 2013;6(4):797-806. PubMed PMID: 23212197.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impaired innate interferon induction in severe therapy resistant atopic asthmatic children. AU - Edwards,M R, AU - Regamey,N, AU - Vareille,M, AU - Kieninger,E, AU - Gupta,A, AU - Shoemark,A, AU - Saglani,S, AU - Sykes,A, AU - Macintyre,J, AU - Davies,J, AU - Bossley,C, AU - Bush,A, AU - Johnston,S L, Y1 - 2012/12/05/ PY - 2012/12/6/entrez PY - 2012/12/6/pubmed PY - 2014/1/17/medline SP - 797 EP - 806 JF - Mucosal immunology JO - Mucosal Immunol VL - 6 IS - 4 N2 - 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. SN - 1935-3456 UR - https://www.unboundmedicine.com/medline/citation/23212197/Impaired_innate_interferon_induction_in_severe_therapy_resistant_atopic_asthmatic_children_ L2 - http://dx.doi.org/10.1038/mi.2012.118 DB - PRIME DP - Unbound Medicine ER -