EphA2 Is a Lung Epithelial Cell Receptor for Pneumocystis β-Glucans
Theodore J Kottom1, Kyle Schaefbauer1, Eva M Carmona1
1Thoracic Diseases Research Unit, Departments of Medicine and Biochemistry, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
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.
Insights
Ephrin type-A receptor 2 (EphA2) binds Pneumocystis fungal beta-glucans on lung epithelial cells. This interaction triggers inflammation, suggesting EphA2 as a target for Pneumocystis therapies.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Pneumocystis interactions with myeloid cells are known, but binding to lung epithelial cells is unclear.
- Ephrin type-A receptor 2 (EphA2) recognizes fungal beta-glucans on lung epithelial cells.
Purpose of the Study:
- To investigate the mechanism of Pneumocystis binding to lung epithelial cells.
- To identify specific receptors involved in this interaction.
Main Methods:
- Investigated EphA2 binding to Pneumocystis beta-glucans.
- Analyzed EphA2 phosphorylation upon Pneumocystis exposure.
- Measured interleukin-6 (IL-6) cytokine levels.
- Utilized EphA2-specific antibodies to block responses.
Main Results:
- EphA2 binds to Pneumocystis beta-glucans, both isolated and on the organism's surface.
- Pneumocystis beta-glucan binding induces EphA2 phosphorylation.
- Interleukin-6 (IL-6) cytokine levels significantly increase in lung epithelial cells exposed to Pneumocystis beta-glucans.
- EphA2 antibody preincubation blocks the IL-6 response.
Conclusions:
- EphA2 is identified as a receptor for Pneumocystis on lung epithelial cells.
- EphA2-mediated signaling contributes to the inflammatory response.
- EphA2 presents a potential target for therapeutic interventions against Pneumocystis infections.
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