Impaired innate interferon induction in severe therapy resistant atopic asthmatic children

Mucosal Immunol. 2013 Jul;6(4):797-806. doi: 10.1038/mi.2012.118. Epub 2012 Dec 5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Asthma / genetics*
  • Asthma / immunology*
  • Asthma / metabolism
  • Child
  • Child, Preschool
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism
  • Female
  • Gene Expression Regulation
  • Humans
  • Hypersensitivity, Immediate / genetics*
  • Hypersensitivity, Immediate / immunology*
  • Hypersensitivity, Immediate / metabolism
  • Immunity, Innate / genetics*
  • Immunoglobulin E / immunology
  • Interferon-Induced Helicase, IFIH1
  • Interferon-beta / genetics
  • Interferon-gamma / genetics
  • Interferons / genetics*
  • Interleukin-8 / biosynthesis
  • Lung / immunology
  • Lung / metabolism
  • Lung / virology
  • Male
  • Picornaviridae Infections / genetics
  • Picornaviridae Infections / immunology
  • Poly I-C / administration & dosage
  • Poly I-C / immunology
  • RNA, Messenger / genetics
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / virology
  • Rhinovirus / immunology
  • Time Factors
  • Toll-Like Receptor 3 / genetics
  • Toll-Like Receptor 3 / metabolism

Substances

  • Interleukin-8
  • RNA, Messenger
  • Toll-Like Receptor 3
  • Immunoglobulin E
  • Interferon-beta
  • Interferon-gamma
  • Interferons
  • DDX58 protein, human
  • IFIH1 protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases
  • Interferon-Induced Helicase, IFIH1
  • Poly I-C