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

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


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.

MeSH terms

  • Animals
  • Candida / immunology*
  • Candidiasis, Oral / immunology*
  • Cell Line
  • Epithelial Cells / immunology*
  • Humans
  • Mice
  • Mice, Knockout
  • Mouth Mucosa / immunology*
  • Receptors, Interleukin-17 / deficiency
  • Receptors, Interleukin-17 / metabolism*
  • Signal Transduction*
  • beta-Defensins / metabolism*


  • Il17ra protein, mouse
  • Receptors, Interleukin-17
  • beta-Defensins
  • beta-defensin 3, mouse