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Original article
Primary airway epithelial cultures from children are highly permissive to respiratory syncytial virus infection
  1. A M Fonceca1,
  2. B F Flanagan2,
  3. R Trinick1,
  4. R L Smyth1,
  5. P S McNamara1
  1. 1Institute of Translational Medicine (Child Health), University of Liverpool, Alder Hey Children's Hospital, Liverpool, Merseyside, UK
  2. 2Institute of infection and global health (Clinical infection, microbiology and immunology), University of Liverpool, Liverpool, Merseyside, UK
  1. Correspondence to Dr Angela Fonceca, Institute of Translational Medicine (Child Health), University of Liverpool, Alder Hey Children's Hospital, Eaton Road, Liverpool L12 2AP, UK; a.fonceca{at}liv.ac.uk

Abstract

Background Respiratory syncytial virus (RSV) infection of airway epithelial cells (AECs) is an important initial event in RSV bronchiolitis. AEC immunological responses are thought to be critical in driving the subsequent inflammation in the airway. This study examined viral replication, cytotoxicity and cytokine production in cultures of primary AECs from children compared with responses to RSV infection in an immortalised epithelial cell line and to those from infants with RSV bronchiolitis.

Methods RSV replication, proinflammatory cytokine responses and cytotoxicity in RSV-infected primary AEC cultures derived from bronchial brushings from the lungs of children were compared with those seen in BEAS-2B cultures, as well as AECs and bronchoalveolar lavage fluid collected from children with and without RSV bronchiolitis.

Results Viral replication, cytotoxicity and inflammatory cytokine production were greater in primary AEC cultures than in BEAS-2B cells. Different response patterns were observed, with RSV infection of primary AEC cultures causing distinct peaks of viral replication and matched cytotoxic responses. Some primary AEC culture immunological responses, such as interleukin 8, were similar in magnitude to those seen in clinical samples from the lungs of children with RSV bronchiolitis. Although variable amounts of RSV were detected by PCR in freshly isolated primary AECs, RSV was not detected by immunocytochemistry.

Conclusion This is one of the first studies to examine comprehensively the responses to RSV infection in primary AEC cultures from children and shows marked differences from those of a commercially available immortalised human cell line but reassuring similarities to results found in vivo. This suggests that future work investigating responses of AECs to RSV infection should use primary AEC cultures.

  • Bronchiolitis
  • airway epithelium
  • cell culture
  • RSV infection
  • broncho-alveolar lavage
  • respiratory infection
  • viral infection
  • cytokine biology
  • paediatric lung disaese
  • paediatric physician

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Footnotes

  • Funding An Intermediate Clinical Fellowship for PSMcN was funded by the Wellcome Trust.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval The Liverpool paediatric research ethics committee approved the study and all samples were collected following written informed consent from parents.

  • Provenance and peer review Not commissioned; externally peer reviewed.