title: Viral and host factors determine innate immune responses in airway epithelial cells from children with wheeze and atopy.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Clinical Medical Virology Centre, The University of Queensland, Herston, Queensland, Australia Sir Albert Sakzewski Virus Research Centre, Queensland Children's Hospital and Health District, Herston, Queensland, Australia Australian Infectious Disease Research Centre, Queensland, Australia.
authors.forename: Kirsten M
authors.initials: KM
authors.lastname: Spann
authors.affiliation: Clinical Medical Virology Centre, The University of Queensland, Herston, Queensland, Australia Sir Albert Sakzewski Virus Research Centre, Queensland Children's Hospital and Health District, Herston, Queensland, Australia Queensland Children's Medical Research Institute, Herston, Queensland, Australia.
authors.forename: Engin
authors.initials: E
authors.lastname: Baturcam
authors.affiliation: Queensland Children's Medical Research Institute, Herston, Queensland, Australia.
authors.forename: Johanna
authors.initials: J
authors.lastname: Schagen
authors.affiliation: Queensland Children's Medical Research Institute, Herston, Queensland, Australia.
authors.forename: Carmen
authors.initials: C
authors.lastname: Jones
authors.affiliation: Clinical Medical Virology Centre, The University of Queensland, Herston, Queensland, Australia Sir Albert Sakzewski Virus Research Centre, Queensland Children's Hospital and Health District, Herston, Queensland, Australia.
authors.forename: Claire P
authors.initials: CP
authors.lastname: Straub
authors.affiliation: Clinical Medical Virology Centre, The University of Queensland, Herston, Queensland, Australia Sir Albert Sakzewski Virus Research Centre, Queensland Children's Hospital and Health District, Herston, Queensland, Australia.
authors.forename: F Maxine
authors.initials: FM
authors.lastname: Preston
authors.affiliation: Queensland Children's Medical Research Institute, Herston, Queensland, Australia.
authors.forename: Linping
authors.initials: L
authors.lastname: Chen
authors.affiliation: Australian Infectious Disease Research Centre, Queensland, Australia School of Biomedical Sciences, University of Queensland, St Lucia, Queensland, Australia.
authors.forename: Simon
authors.initials: S
authors.lastname: Phipps
authors.affiliation: Australian Infectious Disease Research Centre, Queensland, Australia Queensland Children's Medical Research Institute, Herston, Queensland, Australia Global Change Institute, University of Queensland, Queensland, Australia.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Sly
authors.affiliation: Queensland Children's Medical Research Institute, Herston, Queensland, Australia.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Fantino
mesh_terms: D000914:Antibodies, Viral / Q000276:immunology; D001249:Asthma / Q000276:immunology* / Q000473:pathology / Q000821:virology; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology* / Q000473:pathology / Q000821:virology; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D016899:Interferon-beta / Q000276:immunology; D007372:Interferons / Q000276:immunology; D008297:Male; D009297:Nasal Mucosa / Q000276:immunology* / Q000473:pathology / Q000821:virology; D012135:Respiratory Sounds / Q000276:immunology*; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000276:immunology* / Q000302:isolation & purification; D019562:Viral Load
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; C524005:IFNE protein, human; D016899:Interferon-beta; D007372:Interferons
keywords: Airway Epithelium; Asthma; Asthma Mechanisms; Innate Immunity; Respiratory Infection; Viral infection