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EphA2 is a Lung Epithelial Cell Receptor for Pneumocystis β-glucans.
Journal of Infectious Diseases 2021 July 22
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.
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