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

Area of Science:

• Fungal Pathogenesis
• Epithelial Biology
• Zebrafish Models

Background:

• Opportunistic fungal infections are severe and often fatal, particularly after mucosal damage from trauma or chemotherapy.
• Epithelial cell interaction with fungal pathogens is critical for invasion, highlighting the need to strengthen epithelial defenses.

Purpose of the Study:

• To establish a model of fungal infection using inducible epithelial cell loss in larval zebrafish.
• To investigate the role of epithelial damage and repair in fungal invasion and pathogenesis.
• To identify molecular mechanisms and therapeutic targets for mitigating fungal infections.

Main Methods:

• Larval zebrafish model with inducible epithelial cell loss.
• Assessment of fungal attachment, invasion, and larval lethality.
• Transcriptional profiling to identify host response genes.
• Treatment with recombinant human epigen (epidermal growth factor receptor ligand).

Main Results:

• Epithelial cell loss exposed laminin, increasing fungal attachment, invasion, and lethality.
• Fungi with defects in adherence or filamentation showed reduced virulence.
• Mucosal damage significantly upregulated the epidermal growth factor receptor ligand epigen (EPGN).
• Recombinant human EPGN treatment suppressed epithelial cell extrusion, reduced fungal invasion, and enhanced larval survival.

Conclusions:

• Augmenting epithelial restorative capacity is a viable strategy to combat pathogenic fungal invasion.
• Epigen (epidermal growth factor receptor ligand) shows therapeutic potential in mitigating fungal infections by promoting epithelial integrity.
• The zebrafish model provides a valuable platform for studying host-pathogen interactions and testing interventions for opportunistic fungal diseases.