Publication date: Available online 27 October 2016
Source:Cell Host & Microbe
Author(s): 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
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.
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Teaser
IL-17 receptor signaling is required to prevent oropharyngeal candidiasis ("oral thrush") in both mice and humans. Conti et al. demonstrate in mice that IL-17R-dependent antifungal responses in superficial oral epithelial cells (OECs) are critical for protection. Moreover, OECs dominantly control IL-17R-dependent responses through production of the antimicrobial peptide β-defensin 3.http://ift.tt/2e7IPea
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