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Original article
Viral and host factors determine innate immune responses in airway epithelial cells from children with wheeze and atopy
  1. Kirsten M Spann1,2,3,
  2. Engin Baturcam1,2,4,
  3. Johanna Schagen4,
  4. Carmen Jones4,
  5. Claire P Straub1,2,
  6. F Maxine Preston1,2,
  7. Linping Chen4,
  8. Simon Phipps3,5,
  9. Peter D Sly3,4,6,
  10. Emmanuelle Fantino4
  1. 1Clinical Medical Virology Centre, The University of Queensland, Herston, Queensland, Australia
  2. 2Sir Albert Sakzewski Virus Research Centre, Queensland Children's Hospital and Health District, Herston, Queensland, Australia
  3. 3Australian Infectious Disease Research Centre, Queensland, Australia
  4. 4Queensland Children's Medical Research Institute, Herston, Queensland, Australia
  5. 5School of Biomedical Sciences, University of Queensland, St Lucia, Queensland, Australia
  6. 6Global Change Institute, University of Queensland, Queensland, Australia
  1. Correspondence to Dr Kirsten Spann, Sir Albert Sakzewski Virus Research Centre (SASVRC), Block C28, Back Road, Herston 4029, Australia; K.Spann{at}uq.edu.au

Abstract

Background Airway epithelial cells (AEC) from patients with asthma, appear to have an impaired interferon (IFN)-β and -λ response to infection with rhinovirus.

Objectives To determine if impaired IFN responses can be identified in young children at risk of developing asthma due to atopy and/or early life wheeze, and if the site of infection or the infecting virus influence the antiviral response.

Methods Nasal (N) and tracheal (T) epithelial cells (EC) were collected from children categorised with atopy and/or wheeze based on specific IgE to locally common aeroallergens and a questionnaire concerning respiratory health. Submerged primary cultures were infected with respiratory syncytial virus (RSV) or human metapneumovirus (hMPV), and IFN production, inflammatory cytokine expression and viral replication quantified.

Results Nasal epithelial cells (NEC), but not tracheal epithelial cells (TEC), from children with wheeze and/or atopy produced less IFN-β, but not IFN-λ, in response to RSV infection; this was associated with higher viral shedding. However, IFN-regulated factors IRF-7, Mx-1 and CXCL-10, and inflammatory cytokines were not differentially regulated. NECs and TECs from children with wheeze and/or atopy demonstrated no impairment of the IFN response (β or λ) to hMPV infection. Despite this, more hMPV was shed from these cells.

Conclusions AECs from children with wheeze and/or atopy do not have an intrinsic defect in the production of IFN-β or -λ, however, this response is influenced by the infecting virus. Higher viral load is associated with atopy and wheeze suggesting an impaired antiviral response to RSV and hMPV that is not influenced by production of IFNs.

  • Airway Epithelium
  • Asthma
  • Asthma Mechanisms
  • Innate Immunity
  • Respiratory Infection
  • Viral infection

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/

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