EphA2 is a Lung Epithelial Cell Receptor for Pneumocystis β-glucans.

Pneumocystis spp. interaction with myeloid cells is well known, especially in macrophages. Contrary, how the organism binds to lung epithelial cells is incompletely understood. Ephrin type-A receptor (EphA2), has been previously identified as a lung epithelial pattern recognition receptor (PRR) that binds to fungal β-glucans. Herein, we also report that EphA2 can also bind Pneumocystis β-glucans, both in isolated forms and also on exposed surfaces of the organism. Furthermore, binding of Pneumocystis β-glucans resulted in phosphorylation of the EphA2 receptor, which has been shown to be important for downstream proinflammatory response. Indeed, we also show that IL-6 cytokine is significantly increased when lung epithelial cells are exposed to Pneumocystis β-glucans, and that this response could be blocked with preincubation with a specific antibody to EphA2. Our study presents yet another Pneumocystis lung epithelial cell receptor with implications for initial colonization and possible therapeutic intervention.