PT  - JOURNAL ARTICLE
AU  - Marc Swidergall
AU  - Norma V. Solis
AU  - Scott G. Filler
TI  - Epha2, an epithelial cell pattern recognition receptor for fungal β-glucans
AID  - 10.1101/135434
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 135434
4099  - http://biorxiv.org/content/early/2017/05/08/135434.short
4100  - http://biorxiv.org/content/early/2017/05/08/135434.full
AB  - 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 pathogen Candida albicans. Binding of C. albicans to 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 to C. albicans.One Sentence Summary: EphA2 is a pattern recognition receptor that senses fungal β-glucans to induce an inflammatory response in oral epithelial cells.