Macleod, T, Ainscough, JS, Hesse, C et al. (9 more authors) (2020) The proinflammatory cytokine IL-36γ is a global discriminator of harmless microbes and invasive pathogens within epithelial tissues. Cell Reports, 33 (11). 108515. ISSN 2211-1247
Abstract
Epithelial tissues represent vital interfaces between organisms and their environment. As they are constantly exposed to harmful pathogens, innocuous commensals, and environmental microbes, it is essential they sense and elicit appropriate responses toward these different types of microbes. Here, we demonstrate that the epithelial cytokine interleukin-36γ (IL-36γ) acts as a global discriminator of pathogenic and harmless microbes via cell damage and proteolytic activation. We show that intracellular pro-IL-36γ is upregulated by both fungal and bacterial epithelial microbes; yet, it is only liberated from cells, and subsequently processed to its mature, potent, proinflammatory form, by pathogen-mediated cell damage and pathogen-derived proteases. This work demonstrates that IL-36γ senses pathogen-induced cell damage and proteolytic activity and is a key initiator of immune responses and pathological inflammation within epithelial tissues. As an apically located epithelial proinflammatory cytokine, we therefore propose that IL-36γ is critical as the initial discriminator of harmless microbes and invasive pathogens within epithelial tissues.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | Crown Copyright © 2020. This is an open access article under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) (https://creativecommons.org/licenses/by/4.0/) |
Keywords: | epithelial immunity; interleukin-36; IL-36; cytokines; alarmins; pathogen discrimination; proteases; virulence factors; psoriasis; streptococcus |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Molecular Virology (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Experimental Musculoskeletal Medicine (Leeds) |
Funding Information: | Funder Grant number MRC (Medical Research Council) MR/M01942X/1 British Skin Foundation Not Known |
Depositing User: | Symplectic Publications |
Date Deposited: | 04 Nov 2020 14:49 |
Last Modified: | 25 Jun 2023 22:29 |
Status: | Published |
Publisher: | Cell Press |
Identification Number: | 10.1016/j.celrep.2020.108515 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:167538 |