EGF-mediated suppression of cell extrusion during mucosal damage attenuates opportunistic fungal invasion

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dc.citation.articleNumber108896en_US
dc.citation.issueNumber12en_US
dc.citation.journalTitleCell Reportsen_US
dc.citation.volumeNumber34en_US
dc.contributor.authorWurster, Sebastianen_US
dc.contributor.authorRuiz, Oscar E.en_US
dc.contributor.authorSamms, Krystin M.en_US
dc.contributor.authorTatara, Alexander M.en_US
dc.contributor.authorAlbert, Nathaniel D.en_US
dc.contributor.authorKahan, Philip H.en_US
dc.contributor.authorNguyen, Anh Trinhen_US
dc.contributor.authorMikos, Antonios G.en_US
dc.contributor.authorKontoyiannis, Dimitrios P.en_US
dc.contributor.authorEisenhoffer, George T.en_US
dc.date.accessioned2021-04-21T15:46:10Zen_US
dc.date.available2021-04-21T15:46:10Zen_US
dc.date.issued2021en_US
dc.description.abstractSevere and often fatal opportunistic fungal infections arise frequently following mucosal damage caused by trauma or cytotoxic chemotherapy. Interaction of fungal pathogens with epithelial cells that comprise mucosae is a key early event associated with invasion, and, therefore, enhancing epithelial defense mechanisms may mitigate infection. Here, we establish a model of mold and yeast infection mediated by inducible epithelial cell loss in larval zebrafish. Epithelial cell loss by extrusion promotes exposure of laminin associated with increased fungal attachment, invasion, and larval lethality, whereas fungi defective in adherence or filamentation have reduced virulence. Transcriptional profiling identifies significant upregulation of the epidermal growth factor receptor ligand epigen (EPGN) upon mucosal damage. Treatment with recombinant human EPGN suppresses epithelial cell extrusion, leading to reduced fungal invasion and significantly enhanced survival. These data support the concept of augmenting epithelial restorative capacity to attenuate pathogenic invasion of fungi associated with human disease.en_US
dc.identifier.citationWurster, Sebastian, Ruiz, Oscar E., Samms, Krystin M., et al.. "EGF-mediated suppression of cell extrusion during mucosal damage attenuates opportunistic fungal invasion." <i>Cell Reports,</i> 34, no. 12 (2021) Cell Press: https://doi.org/10.1016/j.celrep.2021.108896.en_US
dc.identifier.digital1-s2-0-S2211124721002102-mainen_US
dc.identifier.doihttps://doi.org/10.1016/j.celrep.2021.108896en_US
dc.identifier.urihttps://hdl.handle.net/1911/110287en_US
dc.language.isoengen_US
dc.publisherCell Pressen_US
dc.rightsThis is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).en_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/).en_US
dc.titleEGF-mediated suppression of cell extrusion during mucosal damage attenuates opportunistic fungal invasionen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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