1. IL-17 Receptor Signaling in Oral Epithelial Cells Is Critical for Protection against Oropharyngeal Candidiasis
- Author
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Conti, Heather R, Bruno, Vincent M, Childs, Erin E, Daugherty, Sean, Hunter, Joseph P, Mengesha, Bemnet G, Saevig, Danielle L, Hendricks, Matthew R, Coleman, Bianca M, Brane, Lucas, Solis, Norma, Cruz, J Agustin, Verma, Akash H, Garg, Abhishek V, Hise, Amy G, Richardson, Jonathan P, Naglik, Julian R, Filler, Scott G, Kolls, Jay K, Sinha, Satrajit, and Gaffen, Sarah L
- Subjects
Microbiology ,Medical Microbiology ,Biomedical and Clinical Sciences ,Biological Sciences ,Infectious Diseases ,Dental/Oral and Craniofacial Disease ,Digestive Diseases ,2.1 Biological and endogenous factors ,Aetiology ,Animals ,Candida ,Candidiasis ,Oral ,Cell Line ,Epithelial Cells ,Humans ,Mice ,Mice ,Knockout ,Mouth Mucosa ,Receptors ,Interleukin-17 ,Signal Transduction ,beta-Defensins ,Immunology ,Biochemistry and cell biology ,Medical microbiology - 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.
- Published
- 2016