EphA2 Is a Lung Epithelial Cell Receptor for Pneumocystis β-Glucans

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Abstract
Pneumocystis species interaction with myeloid cells is well known, especially in macrophages; however, how the organism binds to lung epithelial cells is incompletely understood. Ephrin type-A receptor 2 (EphA2) has been previously identified as a lung epithelial pattern recognition receptor 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 interleukin 6 cytokine is significantly increased when lung epithelial cells are exposed to Pneumocystis β-glucans, and that this response could be blocked by preincubation with a specific antibody to EphA2. Our study presents another Pneumocystis lung epithelial cell receptor with implications for initial colonization and possible therapeutic intervention.
Funding Information
  • Mayo Foundation
  • Walter and Leonore Annenberg Foundation
  • National Institutes of Health (R01-HL62150)

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