Details

Autor(en) / Beteiligte

• 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.

Titel

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

Ist Teil von

• Cell host & microbe, 2016-11, Vol.20 (5), p.606-617

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2016

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• 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. [Display omitted] •Human and murine oral epithelial cells show concordant responses to C. albicans•IL-17R signaling in the oral epithelium is necessary for defense against candidiasis•IL-17R signaling in oral epithelial cells is a major driver of β-defensin expression•β-defensin-3-deficient mice are susceptible to oral candidiasis 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.