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, 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.

• Authors: Heather R Conti, Vincent M Bruno, Erin E Childs, Sean Daugherty, Joseph P Hunter, Bemnet G Mengesha, Danielle L Saevig, Matthew R Hendricks, Bianca M Coleman, Lucas Brane, Norma Solis, J Agustin Cruz, Akash H Verma, Abhishek V Garg, Amy G Hise, Jonathan P Richardson, Julian R Naglik, Scott G Filler, Jay K Kolls, Satrajit Sinha, Sarah L Gaffen
• Journal: Cell host & microbe (Cell Host Microbe) Vol. 20 Issue 5 Pg. 606-617 (Nov 09 2016) ISSN: 1934-6069 [Electronic] United States
• PMID: 27923704 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

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

Topics

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