Epitope shaving promotes fungal immune evasion
dc.contributor.author | Childers, DS | |
dc.contributor.author | Mol Avelar, G | |
dc.contributor.author | Bain, JM | |
dc.contributor.author | Pradhan1, A | |
dc.contributor.author | Larcombe, DE | |
dc.contributor.author | Netea, MG | |
dc.contributor.author | Erwig, LP | |
dc.contributor.author | Gow, NAR | |
dc.contributor.author | Brown, AJP | |
dc.date.accessioned | 2020-06-12T07:07:00Z | |
dc.date.issued | 2020-07-07 | |
dc.description.abstract | The cell wall provides a major physical interface between fungal pathogens and their mammalian host. This extracellular armour is critical for fungal cell homeostasis and survival. Fungal-specific cell wall moieties, such as β-1,3-glucan, are recognised as pathogen-associated molecular patterns (PAMPs) that activate immune-mediated clearance mechanisms. We have reported that the opportunistic human fungal pathogen, Candida albicans, masks β-1,3-glucan following exposure to lactate, hypoxia or iron depletion. However, the precise mechanism(s) by which C. albicans masks β-1,3-glucan have remained obscure. Here we identify a secreted exoglucanase, Xog1, that is induced in response to lactate or hypoxia. Xog1 functions downstream of the lactate-induced β-glucan “masking” pathway to promote β-1,3-glucan “shaving”. Inactivation of XOG1 blocks most, but not all β-1,3-glucan masking in response to lactate, suggesting that other activities contribute to this phenomenon. Nevertheless, XOG1 deletion attenuates the lactate-induced reductions in phagocytosis and cytokine stimulation normally observed for wild type cells. We also demonstrate that the pharmacological inhibition of exoglucanases undermines β-glucan shaving, enhances the immune visibility of the fungus, and attenuates its virulence. Our study establishes a new mechanism underlying environmentally-induced PAMP remodelling that can be manipulated pharmacologically to influence immune recognition and infection outcomes. | en_GB |
dc.description.sponsorship | Medical Research Council (MRC) | en_GB |
dc.description.sponsorship | Wellcome Trust | en_GB |
dc.description.sponsorship | University of Aberdeen | en_GB |
dc.description.sponsorship | European Research Council (ERC) | en_GB |
dc.description.sponsorship | Netherlands Organization for Scientific Research | en_GB |
dc.identifier.citation | Vol. 11 (4), article e00984-20 | en_GB |
dc.identifier.doi | 10.1128/mBio.00984-20 | |
dc.identifier.grantnumber | MR/M026663/1 | en_GB |
dc.identifier.grantnumber | 097377 | en_GB |
dc.identifier.grantnumber | 075470 | en_GB |
dc.identifier.grantnumber | 086827 | en_GB |
dc.identifier.grantnumber | 093378 | en_GB |
dc.identifier.grantnumber | 099197 | en_GB |
dc.identifier.grantnumber | 101873 | en_GB |
dc.identifier.grantnumber | 102705 | en_GB |
dc.identifier.grantnumber | 200208 | en_GB |
dc.identifier.grantnumber | MR/N006364/1 | en_GB |
dc.identifier.grantnumber | 833247 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/121390 | |
dc.language.iso | en | en_GB |
dc.publisher | American Society for Microbiology | en_GB |
dc.rights | © 2020 Childers et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. | |
dc.subject | Candida albicans | en_GB |
dc.subject | cell wall | en_GB |
dc.subject | Xog1 exoglucanase | en_GB |
dc.subject | β-glucan shaving | en_GB |
dc.subject | immune evasion | en_GB |
dc.subject | castanospermine | en_GB |
dc.subject | virulence | en_GB |
dc.title | Epitope shaving promotes fungal immune evasion | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2020-06-12T07:07:00Z | |
dc.identifier.issn | 2150-7511 | |
dc.description | This is the final version. Available on open access from the American Society for Microbiology via the DOI in this record | en_GB |
dc.description | Data availability. The data supporting the findings in this study are available within the paper and accompanying supplementary files. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (44) partner repository with the dataset identifiers: PXD018027and PXD018044. The source data for cytometry, enzyme activity, and immune interaction studies are provided as a source data file. | en_GB |
dc.identifier.journal | mBio | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2020-06-10 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2020-06-10 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2020-06-11T14:27:35Z | |
refterms.versionFCD | AM | |
refterms.dateFOA | 2020-08-14T12:55:01Z | |
refterms.panel | A | en_GB |
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This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.