Non-canonical IL‑22 receptor signaling remodels the oral mucosal barrier during Candida albicans immunosurveillance

Abstract

Abstract Mucosal barrier integrity is vital for homeostasis with commensal organisms while preventing pathogen invasion. Here we show that fungal-induced immunosurveillance enhances resistance to fungal outgrowth and tissue invasion by remodeling the oral mucosal epithelial barrier in mouse models of adult and neonatal Candida albicans colonization. Epithelial subset expansion and tissue remodeling are dependent on interleukin-22 and signal transducer and activator of transcription 3 signaling, through a non-canonical receptor complex composed of glycoprotein 130 coupled with the interleukin-22 receptor subunit alpha-1 and the interleukin-10 receptor subunit beta. Epithelial proliferation enhanced antifungal host defenses through the upregulation of antimicrobial peptide expression. Immunosurveillance-induced epithelial remodeling is restricted to the oral mucosa, whereas barrier architecture is reset once fungal-specific immunity developed. Collectively, these findings identify fungal-induced transient mucosal remodeling as a critical determinant of resistance to mucosal fungal infection during early stages of microbial colonization.