title: Dectin-1 promotes fungicidal activity of human neutrophils.
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 (beta-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 beta-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 beta-glucan and GE2 inhibited phagocytosis and killing of Candida albicans by PMN (inhibition of killing was 54.8% for beta-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.
authors.affiliation: Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
authors.forename: Adam D
authors.initials: AD
authors.lastname: Kennedy
authors.forename: Janet A
authors.initials: JA
authors.lastname: Willment
authors.forename: David W
authors.initials: DW
authors.lastname: Dorward
authors.forename: David L
authors.initials: DL
authors.lastname: Williams
authors.forename: Gordon D
authors.initials: GD
authors.lastname: Brown
authors.forename: Frank R
authors.initials: FR
authors.lastname: DeLeo
mesh_terms: D002176:Candida albicans / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D037181:Lectins, C-Type; D008565:Membrane Proteins / Q000276:immunology*; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D009419:Nerve Tissue Proteins / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology* / Q000648:ultrastructure; D010587:Phagocytosis / Q000276:immunology; D000099181:Dectin-1
chemical_list: D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D000099181:Dectin-1