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

dc.citation.articleNumber108896
dc.citation.issueNumber12
dc.citation.journalTitleCell Reports
dc.citation.volumeNumber34
dc.contributor.authorWurster, Sebastian
dc.contributor.authorRuiz, Oscar E.
dc.contributor.authorSamms, Krystin M.
dc.contributor.authorTatara, Alexander M.
dc.contributor.authorAlbert, Nathaniel D.
dc.contributor.authorKahan, Philip H.
dc.contributor.authorNguyen, Anh Trinh
dc.contributor.authorMikos, Antonios G.
dc.contributor.authorKontoyiannis, Dimitrios P.
dc.contributor.authorEisenhoffer, George T.
dc.date.accessioned2021-04-21T15:46:10Z
dc.date.available2021-04-21T15:46:10Z
dc.date.issued2021
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.
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.
dc.identifier.digital1-s2-0-S2211124721002102-main
dc.identifier.doihttps://doi.org/10.1016/j.celrep.2021.108896
dc.identifier.urihttps://hdl.handle.net/1911/110287
dc.language.isoeng
dc.publisherCell Press
dc.rightsThis is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/).
dc.titleEGF-mediated suppression of cell extrusion during mucosal damage attenuates opportunistic fungal invasion
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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