Non-canonical IL‑22 receptor signaling remodels the oral mucosal barrier during Candida albicans immunosurveillance
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.
Authors
- Scott G. Filler (ORCID: https://orcid.org/0000-0001-7278-3700)
- Nicolas Millet (ORCID: https://orcid.org/0000-0002-4644-7153)
- Brian M. Peters (ORCID: https://orcid.org/0000-0002-0445-2077)
- Sarah L. Gaffen (ORCID: https://orcid.org/0000-0001-8511-2041)
- Melissa E. Cook (ORCID: https://orcid.org/0000-0002-2336-956X)
- Asia S. Wildeman (ORCID: https://orcid.org/0009-0009-2082-9741)
- Jinendiran Sekar (ORCID: https://orcid.org/0000-0002-8044-1628)
- Nicholas Jendzjowsky (ORCID: https://orcid.org/0000-0002-4342-1839)
- Marc Swidergall (ORCID: https://orcid.org/0000-0002-5261-6267)
- Norma V. Solis (ORCID: https://orcid.org/0000-0001-5163-2110)
- Amirhossein Davari (ORCID: https://orcid.org/0000-0002-7492-9299)
- Antoine Millet (ORCID: https://orcid.org/0000-0001-6195-608X)
- Felix E. Y. Aggor
- Michail S. Lionakis
- Jian Miao
Institutions
- Inserm (FR)
- University of Tennessee Health Science Center (US)
- University of California, Los Angeles (US)
- University of Pittsburgh (US)
- UCLA Medical Center (US)
- Sorbonne Université (FR)
- National Institute of Allergy and Infectious Diseases (US)
- Centre de Recherche Saint-Antoine (FR)
- Harbor–UCLA Medical Center (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-04-03
- DOI
- https://doi.org/10.1038/s41467-026-71459-z
- Primary Topic
- Antifungal resistance and susceptibility
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- California Institute for Regenerative Medicine
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- Tulane University
- Dana-Farber/Harvard Cancer Center
- Ministerio de Economía y Competitividad
- Universität Zürich
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases
- National Institute of Dental and Craniofacial Research
- NHLBI Division of Intramural Research