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dc.contributor.authorRowley, Jessica; email: j.rowley@imperial.ac.uk
dc.contributor.authorNamvar, Sara; orcid: 0000-0001-5571-368X; email: s.namvar@salford.ac.uk
dc.contributor.authorGago, Sara; orcid: 0000-0002-7027-4598; email: sara.gago-2@manchester.ac.uk
dc.contributor.authorLabram, Briony; email: briony.labram@nc3rs.org.uk
dc.contributor.authorBowyer, Paul; email: paul.bowyer@manchester.ac.uk
dc.contributor.authorRichardson, Malcolm D.; orcid: 0000-0001-5672-9552; email: Malcolm.Richardson@manchester.ac.uk
dc.contributor.authorHerrick, Sarah E.; orcid: 0000-0002-9085-5664; email: Sarah.Herrick@manchester.ac.uk
dc.date.accessioned2021-06-12T00:17:55Z
dc.date.available2021-06-12T00:17:55Z
dc.date.issued2021-06-10
dc.identifierhttps://chesterrep.openrepository.com/bitstream/handle/10034/624916/jof-07-00468.pdf?sequence=2
dc.identifierhttps://chesterrep.openrepository.com/bitstream/handle/10034/624916/additional-files.zip?sequence=3
dc.identifierhttps://chesterrep.openrepository.com/bitstream/handle/10034/624916/jof-07-00468.xml?sequence=4
dc.identifier.citationJournal of Fungi, volume 7, issue 6, page e468
dc.identifier.urihttp://hdl.handle.net/10034/624916
dc.descriptionFrom MDPI via Jisc Publications Router
dc.descriptionHistory: accepted 2021-06-03, pub-electronic 2021-06-10
dc.descriptionPublication status: Published
dc.description.abstractAspergillus fumigatus is an important human respiratory mould pathogen. In addition to a barrier function, airway epithelium elicits a robust defence against inhaled A. fumigatus by initiating an immune response. The manner by which A. fumigatus initiates this response and the reasons for the immunological heterogeneity with different isolates are unclear. Both direct fungal cell wall–epithelial cell interaction and secretion of soluble proteases have been proposed as possible mechanisms. Our aim was to determine the contribution of fungal proteases to the induction of epithelial IL-6 and IL-8 in response to different A. fumigatus isolates. Airway epithelial cells were exposed to conidia from a low or high protease-producing strain of A. fumigatus, and IL-6 and IL-8 gene expression and protein production were quantified. The role of proteases in cytokine production was further determined using specific protease inhibitors. The proinflammatory cytokine response correlated with conidia germination and hyphal extension. IL-8 induction was significantly reduced in the presence of matrix metalloprotease or cysteine protease inhibitors. With a high protease-producing strain of A. fumigatus, IL-6 release was metalloprotease dependent. Dectin-1 antagonism also inhibited the production of both cytokines. In conclusion, A. fumigatus-secreted proteases mediate a proinflammatory response by airway epithelial cells in a strain-dependent manner.
dc.languageen
dc.publisherMDPI
dc.rightsLicence for this article: https://creativecommons.org/licenses/by/4.0/
dc.sourceeissn: 2309-608X
dc.subjectAspergillus fumigatus
dc.subjectairway epithelium
dc.subjectproteases
dc.subjectinflammatory cytokines
dc.subjectfungal lung disease
dc.titleDifferential Proinflammatory Responses to Aspergillus fumigatus by Airway Epithelial Cells In Vitro Are Protease Dependent
dc.typearticle
dc.date.updated2021-06-12T00:17:55Z
dc.date.accepted2021-06-03


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