title: IL-17 Receptor Signaling in Oral Epithelial Cells Is Critical for Protection against Oropharyngeal Candidiasis.
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, Il17raΔK13mice exhibited fungal loads and weight loss indistinguishable from Il17ra-/-mice. Susceptibility in Il17raΔK13mice 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.
authors.affiliation: 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.
authors.forename: Heather R
authors.initials: HR
authors.lastname: Conti
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Bruno
authors.affiliation: Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Childs
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Daugherty
authors.affiliation: Department of Biological Sciences, University of Toledo, Toledo, OH 43606, USA.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Hunter
authors.affiliation: Department of Biological Sciences, University of Toledo, Toledo, OH 43606, USA.
authors.forename: Bemnet G
authors.initials: BG
authors.lastname: Mengesha
authors.affiliation: Department of Biological Sciences, University of Toledo, Toledo, OH 43606, USA.
authors.forename: Danielle L
authors.initials: DL
authors.lastname: Saevig
authors.affiliation: Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Hendricks
authors.affiliation: Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Bianca M
authors.initials: BM
authors.lastname: Coleman
authors.affiliation: Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Lucas
authors.initials: L
authors.lastname: Brane
authors.affiliation: Division of Infectious Diseases, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
authors.forename: Norma
authors.initials: N
authors.lastname: Solis
authors.affiliation: Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: J Agustin
authors.initials: JA
authors.lastname: Cruz
authors.affiliation: Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Akash H
authors.initials: AH
authors.lastname: Verma
authors.affiliation: Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Abhishek V
authors.initials: AV
authors.lastname: Garg
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA; Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH 44106, USA.
authors.forename: Amy G
authors.initials: AG
authors.lastname: Hise
authors.affiliation: Department of Mucosal and Salivary Biology, King's College London, London SE1 1UL, UK.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Richardson
authors.affiliation: Department of Mucosal and Salivary Biology, King's College London, London SE1 1UL, UK.
authors.forename: Julian R
authors.initials: JR
authors.lastname: Naglik
authors.affiliation: Division of Infectious Diseases, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
authors.forename: Scott G
authors.initials: SG
authors.lastname: Filler
authors.affiliation: Richard King Mellon Foundation for Pediatric Research, Children's Hospital of UPMC, Pittsburgh, PA 15224, USA.
authors.forename: Jay K
authors.initials: JK
authors.lastname: Kolls
authors.affiliation: Department of Biochemistry, University at Buffalo, State University of New York, Buffalo, NY 14203, USA.
authors.forename: Satrajit
authors.initials: S
authors.lastname: Sinha
authors.affiliation: 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.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Gaffen
mesh_terms: D000818:Animals; D002175:Candida / Q000276:immunology*; D002180:Candidiasis, Oral / Q000276:immunology*; D002460:Cell Line; D004847:Epithelial Cells / Q000276:immunology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009061:Mouth Mucosa / Q000276:immunology*; D053722:Receptors, Interleukin-17 / Q000172:deficiency / Q000378:metabolism*; D015398:Signal Transduction; D023083:beta-Defensins / Q000378:metabolism*
chemical_list: C491673:Il17ra protein, mouse; D053722:Receptors, Interleukin-17; D023083:beta-Defensins; C540070:beta-defensin 3, mouse