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Previous influenza infection exacerbates allergen specific response and impairs airway barrier integrity in pre‐sensitized mice


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Looi, K, Larcombe, AN, Perks, KL, Berry, LJ, Zosky, GR ORCID: 0000-0001-9039-0302, Rigby, P, Knight, DA, Kicic, A and Stick, SM 2021 , 'Previous influenza infection exacerbates allergen specific response and impairs airway barrier integrity in pre‐sensitized mice' , International Journal of Molecular Sciences, vol. 22, no. 16 , pp. 1-15 , doi: 10.3390/ijms22168790.

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In this study we assessed the effects of antigen exposure in mice pre-sensitized with allergen following viral infection on changes in lung function, cellular responses and tight junction expression. Female BALB/c mice were sensitized to ovalbumin and infected with influenza A before receiving a second ovalbumin sensitization and challenge with saline, ovalbumin (OVA) or house dust mite (HDM). Fifteen days post-infection, bronchoalveolar inflammation, serum antibodies, responsiveness to methacholine and barrier integrity were assessed. There was no effect of infection alone on bronchoalveolar lavage cellular inflammation 15 days post-infection; however, OVA or HDM challenge resulted in increased bronchoalveolar inflammation dominated by eosinophils/neutrophils or neutrophils, respectively. Previously infected mice had higher serum OVA-specific IgE compared with uninfected mice. Mice previously infected, sensitized and challenged with OVA were most responsive to methacholine with respect to airway resistance, while HDM challenge caused significant increases in both tissue damping and tissue elastance regardless of previous infection status. Previous influenza infection was associated with decreased claudin-1 expression in all groups and decreased occludin expression in OVA or HDM-challenged mice. This study demonstrates the importance of the respiratory epithelium in pre-sensitized individuals, where influenza-infection-induced barrier disruption resulted in increased systemic OVA sensitization and downstream effects on lung function.

Item Type: Article
Authors/Creators:Looi, K and Larcombe, AN and Perks, KL and Berry, LJ and Zosky, GR and Rigby, P and Knight, DA and Kicic, A and Stick, SM
Keywords: house dust mite, lung function, BALB/c mice, influenza, tight junctions, epithelial barrier integrity
Journal or Publication Title: International Journal of Molecular Sciences
Publisher: Molecular Diversity Preservation International
ISSN: 1422-0067
DOI / ID Number: 10.3390/ijms22168790
Copyright Information:

Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons 4.0 International (CC BY 4.0) license (

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