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Differential proinflammatory responses to Aspergillus fumigatus by airway epithelial cells in vitro are protease dependent

Rowley, J; Namvar, S; Gago, S; Labram, B; Bowyer, P; Richardson, MD; Herrick, SE

Differential proinflammatory responses to Aspergillus fumigatus by airway epithelial cells in vitro are protease dependent Thumbnail


Authors

J Rowley

S Gago

B Labram

P Bowyer

MD Richardson

SE Herrick



Contributors

R Ben-Ami
Editor

Abstract

Aspergillus 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.

Citation

Rowley, J., Namvar, S., Gago, S., Labram, B., Bowyer, P., Richardson, M., & Herrick, S. (2021). Differential proinflammatory responses to Aspergillus fumigatus by airway epithelial cells in vitro are protease dependent. Journal of Fungi, 7(6), e468. https://doi.org/10.3390/jof7060468

Journal Article Type Article
Acceptance Date Jun 3, 2021
Publication Date Jun 10, 2021
Deposit Date Jun 14, 2021
Publicly Available Date Jun 14, 2021
Journal Journal of Fungi
Print ISSN 2309-608X
Publisher MDPI
Volume 7
Issue 6
Pages e468
DOI https://doi.org/10.3390/jof7060468
Publisher URL https://doi.org/10.3390/jof7060468
Related Public URLs https://www.mdpi.com/journal/jof
Additional Information Additional Information : Jessica Rowley and Sara Namvar are joint first authors of this work and contributed equally to it.
Funders : Fungal Infection Trust;National Aspergillosis Centre;University Hospital of South Manchester NHS Foundation Trust;Medical Research Council (MRC)

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