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Cell Host Microbe. 2016 Nov 9;20(5):606-617. doi: 10.1016/j.chom.2016.10.001. Epub 2016 Oct 27.

IL-17 Receptor Signaling in Oral Epithelial Cells Is Critical for Protection against Oropharyngeal Candidiasis.

Author information

1
Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Biological Sciences, University of Toledo, Toledo, OH 43606, USA. Electronic address: heather.conti@utoledo.edu.
2
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
3
Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
4
Department of Biological Sciences, University of Toledo, Toledo, OH 43606, USA.
5
Division of Infectious Diseases, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
6
Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA; Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH 44106, USA.
7
Department of Mucosal and Salivary Biology, King's College London, London SE1 1UL, UK.
8
Richard King Mellon Foundation for Pediatric Research, Children's Hospital of UPMC, Pittsburgh, PA 15224, USA.
9
Department of Biochemistry, University at Buffalo, State University of New York, Buffalo, NY 14203, USA.
10
Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Mucosal and Salivary Biology, King's College London, London SE1 1UL, UK. Electronic address: sarah.gaffen@pitt.edu.

Abstract

Signaling through the IL-17 receptor (IL-17R) is required to prevent oropharyngeal candidiasis (OPC) in mice and humans. However, the IL-17-responsive cell type(s) that mediate protection are unknown. Using radiation chimeras, we were able to rule out a requirement for IL-17RA in the hematopoietic compartment. We saw remarkable concordance of IL-17-controlled gene expression in C. albicans-infected human oral epithelial cells (OECs) and in tongue tissue from mice with OPC. To interrogate the role of the IL-17R in OECs, we generated mice with conditional deletion of IL-17RA in superficial oral and esophageal epithelial cells (Il17raΔK13). Following oral Candida infection, Il17raΔK13 mice exhibited fungal loads and weight loss indistinguishable from Il17ra-/- mice. Susceptibility in Il17raΔK13 mice correlated with expression of the antimicrobial peptide β-defensin 3 (BD3, Defb3). Consistently, Defb3-/- mice were susceptible to OPC. Thus, OECs dominantly control IL-17R-dependent responses to OPC through regulation of BD3 expression.

PMID:
27923704
PMCID:
PMC5147498
DOI:
10.1016/j.chom.2016.10.001
[Indexed for MEDLINE]
Free PMC Article

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