Epha2, An Epithelial Cell Pattern Recognition Receptor For Fungal β-Glucans

Abstract

AbstractOral 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 {beta}-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 {beta}-glucans that senses epithelial cell fungal burden and is required for the maximal mucosal inflammatory response to C. albicans.\n\nOne Sentence SummaryEphA2 is a pattern recognition receptor that senses fungal {beta}-glucans to induce an inflammatory response in oral epithelial cells.