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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. © The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Citation

Theodore J Kottom, Kyle Schaefbauer, Eva M Carmona, Andrew H Limper. EphA2 Is a Lung Epithelial Cell Receptor for Pneumocystis β-Glucans. The Journal of infectious diseases. 2022 Feb 01;225(3):525-530

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PMID: 34289046

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