Dectin-1 promotes fungicidal activity of human neutrophils

Adam D Kennedy, Janet A Willment, David W Dorward, David L Williams, Gordon D Brown, Frank R DeLeo

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87 Citations (Scopus)

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 languageEnglish
Pages (from-to)467-478
Number of pages12
JournalEuropean Journal of Immunology
Volume37
Issue number2
Early online date17 Jan 2007
DOIs
Publication statusPublished - Feb 2007

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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

Cite this

Kennedy, A. D., Willment, J. A., Dorward, D. W., Williams, D. L., Brown, G. D., & DeLeo, F. R. (2007). Dectin-1 promotes fungicidal activity of human neutrophils. European Journal of Immunology, 37(2), 467-478. https://doi.org/10.1002/eji.200636653