Cell host & microbe · 2016
IL-17 Receptor Signaling in Oral Epithelial Cells Is Critical for Protection against Oropharyngeal Candidiasis.
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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, Gaffen Sarah L
Аннотация
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.