Abstract
Human polymorphonuclear leukocytes (PMN) are a first line of defense against fungal infections. PMN express numerous pattern recognition receptors (PRR) that facilitate identification of invading microorganisms and ultimately promote resolution of disease. Dectin-1 (β-glucan receptor) is a PRR expressed on several cell types and has been studied on monocytes and macrophages. However, the role played by dectin-1 in the recognition and killing of fungi by PMN is unknown. We investigated the ability of dectin-1 to mediate human PMN phagocytosis and fungicidal activity. Dectin-1 was expressed on the surface of PMN from all subjects tested (n=29) and in an intracellular compartment that co-sedimented with azurophilic granules in Percoll density gradients. Soluble β-glucan and mAb GE2 (anti-dectin-1) inhibited binding and phagocytosis of zymosan by human PMN (e.g., ingestion was inhibited 40.1% by 30 min, p<0.001), and blocked reactive oxygen species production. Notably, soluble β-glucan and GE2 inhibited phagocytosis and killing of Candida albicans by PMN (inhibition of killing was 54.8% for β-glucan and 36.2% for GE2, p<0.01). Our results reveal a mechanism whereby PMN dectin-1 plays a key role in the recognition and killing of fungal pathogens by the innate immune system.
Original language | English |
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Pages (from-to) | 467-478 |
Number of pages | 12 |
Journal | European Journal of Immunology |
Volume | 37 |
Issue number | 2 |
Early online date | 17 Jan 2007 |
DOIs | |
Publication status | Published - Feb 2007 |
Keywords
- Candida albicans
- Cytotoxicity, Immunologic
- Electrophoresis, Polyacrylamide Gel
- Flow Cytometry
- Fluorescent Antibody Technique
- Humans
- Immunoblotting
- Membrane Proteins
- Microscopy, Confocal
- Microscopy, Electron, Scanning
- Microscopy, Electron, Transmission
- Nerve Tissue Proteins
- Neutrophils
- Phagocytosis
- Cell Surface Molecules
- Fungal
- Human