Dectin-1 promotes fungicidal activity of human neutrophils

Eur J Immunol. 2007 Feb;37(2):467-78. doi: 10.1002/eji.200636653.

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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Candida albicans / immunology*
  • Cytotoxicity, Immunologic*
  • Electrophoresis, Polyacrylamide Gel
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Humans
  • Immunoblotting
  • Lectins, C-Type
  • Membrane Proteins / immunology*
  • Microscopy, Confocal
  • Microscopy, Electron, Scanning
  • Microscopy, Electron, Transmission
  • Nerve Tissue Proteins / immunology*
  • Neutrophils / immunology*
  • Neutrophils / microbiology*
  • Neutrophils / ultrastructure
  • Phagocytosis / immunology

Substances

  • Lectins, C-Type
  • Membrane Proteins
  • Nerve Tissue Proteins
  • dectin 1