Impaired innate interferon induction in severe therapy resistant atopic asthmatic children

M. R. Edwards (Lead / Corresponding author), N. Regamey, M. Vareille, E. Kieninger, A. Gupta, A. Shoemark, S. Saglani, A. Sykes, J. MacIntyre, J. Davies, C. Bossley, A. Bush, S. L. Johnston

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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.

Original languageEnglish
Pages (from-to)797-806
Number of pages10
JournalMucosal Immunology
Issue number4
Early online date5 Dec 2012
Publication statusPublished - Jul 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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