PUBLICATION
EGF-mediated suppression of cell extrusion during mucosal damage attenuates opportunistic fungal invasion
- Authors
- Wurster, S., Ruiz, O.E., Samms, K.M., Tatara, A.M., Albert, N.D., Kahan, P.H., Nguyen, A.T., Mikos, A.G., Kontoyiannis, D.P., Eisenhoffer, G.T.
- ID
- ZDB-PUB-210325-14
- Date
- 2021
- Source
- Cell Reports 34: 108896 (Journal)
- Registered Authors
- Eisenhoffer, George, Kahan, Philip, Nguyen, Anh Trinh, Ruiz, Oscar E., Samms, Krystin
- Keywords
- EGF signaling, cell extrusion, epitheli, fungi, zebrafish
- Datasets
- GEO:GSE140839
- MeSH Terms
-
- Animals
- Epidermal Growth Factor/pharmacology*
- Epigen/pharmacology
- Epithelial Cells/drug effects
- Epithelial Cells/microbiology
- Epithelial Cells/ultrastructure
- Humans
- Hyphae/drug effects
- Hyphae/growth & development
- Larva/microbiology
- Models, Biological
- Mucous Membrane/drug effects
- Mucous Membrane/microbiology*
- Mucous Membrane/pathology*
- Neutrophils/drug effects
- Neutrophils/metabolism
- Recombinant Proteins/pharmacology
- Rhizopus/pathogenicity*
- Rhizopus/ultrastructure
- Spores, Fungal/drug effects
- Spores, Fungal/physiology
- Time Factors
- Zebrafish/microbiology
- PubMed
- 33761358 Full text @ Cell Rep.
Citation
Wurster, S., Ruiz, O.E., Samms, K.M., Tatara, A.M., Albert, N.D., Kahan, P.H., Nguyen, A.T., Mikos, A.G., Kontoyiannis, D.P., Eisenhoffer, G.T. (2021) EGF-mediated suppression of cell extrusion during mucosal damage attenuates opportunistic fungal invasion. Cell Reports. 34:108896.
Abstract
Severe 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping