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Local dornase alfa treatment reduces NETs-induced airway obstruction during severe RSV infection
  1. Bart Cortjens1,
  2. Rineke de Jong2,
  3. Judith G Bonsing2,
  4. Job B M van Woensel1,
  5. Adriaan F G Antonis2,
  6. Reinout A Bem1
  1. 1Paediatric Intensive Care, Emma Children's Hospital, Amsterdam, The Netherlands
  2. 2Wageningen University and Research, Bioveterinary Research, Lelystad, The Netherlands
  1. Correspondence to Bart Cortjens, Paediatric Intensive Care, Emma Children's Hospital, Meibergdreef 9, Amsterdam 1100 DD, The Netherlands ; b.cortjens{at}amc.nl

Abstract

Respiratory syncytial virus (RSV) infection is characterised by airway obstruction with mucus plugs, containing DNA networks in the form of neutrophil extracellular traps (NETs). We investigated the effect of dornase alfa on histopathological NETs-induced airway obstruction and viral load in an age-relevant calf model of severe bovine RSV disease. As compared with the control animals, dornase alfa treatment resulted in a strong reduction of NETs-induced airway obstruction. Viral load in the lower respiratory tract was not different between the two groups. We conclude that NETs form a relevant target for treatment of airway obstruction in severe RSV disease.

  • respiratory infection
  • infection control
  • innate immunity
  • neutrophil biology
  • paediatric lung disaese
  • viral infection

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Footnotes

  • Contributors BC, JBMvW, RdJ, AFA and RAB designed the study. BC, RdJ, JGB and AFA conceived and carried out the animal experiments. BC, RdJ and JGB carried out the BAL measurements and immunohistochemistry and analysed the data. BC, RdJ, AFA, JBMvW and RAB interpreted the results. All authors were involved in writing the paper and had final approval of the submitted and published versions.

  • Funding This work was supported by the Emma Children's Hospital Support Foundation [CC200001], and the Amsterdam Economic Board [EZ1311 ALOHA RSV].

  • Competing interests None declared.

  • Ethics approval This study was conducted under legislation ofthe Dutch Central Authority for Scientific procedures on Animals and after approved of the Body of Animal Welfare of Wageningen University and Research.

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

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