Epha2, an epithelial cell pattern recognition receptor for fungal β-glucans

Oral epithelial cells discriminate between pathogenic and non-pathogenic stimuli, and only induce an inflammatory response when they are exposed to high levels of a potentially harmful microorganism. The pattern recognition receptors (PRRs) in epithelial cells that mediate this differential response are poorly understood. Here, we demonstrate that the ephrin type-A receptor 2 (EphA2) is an oral epithelial cell PRR that binds to exposed β-glucans on the surface of the fungal pathogenCandida albicans. Binding ofC. albicansto EphA2 on oral epithelial cells activates signal transducer and activator of transcription 3 (Stat3) and mitogen-activated protein kinase signaling in an inoculum-dependent manner, and is required for induction of a pro-inflammatory and antifungal response. Inhibition of EphA2 in mice decreases IL-17 signaling during oropharyngeal candidiasis, resulting in increased oral fungal burden and fungal dissemination. Our study reveals that EphA2 functions as PRR for β-glucans that senses epithelial cell fungal burden and is required for the maximal mucosal inflammatory response toC. albicans.One Sentence Summary:EphA2 is a pattern recognition receptor that senses fungal β-glucans to induce an inflammatory response in oral epithelial cells.