Activation of the innate immune receptor Dectin-1 upon formation of a 'phagocytic synapse'

Nature. 2011 Apr 28;472(7344):471-5. doi: 10.1038/nature10071.


Innate immune cells must be able to distinguish between direct binding to microbes and detection of components shed from the surface of microbes located at a distance. Dectin-1 (also known as CLEC7A) is a pattern-recognition receptor expressed by myeloid phagocytes (macrophages, dendritic cells and neutrophils) that detects β-glucans in fungal cell walls and triggers direct cellular antimicrobial activity, including phagocytosis and production of reactive oxygen species (ROS). In contrast to inflammatory responses stimulated upon detection of soluble ligands by other pattern-recognition receptors, such as Toll-like receptors (TLRs), these responses are only useful when a cell comes into direct contact with a microbe and must not be spuriously activated by soluble stimuli. In this study we show that, despite its ability to bind both soluble and particulate β-glucan polymers, Dectin-1 signalling is only activated by particulate β-glucans, which cluster the receptor in synapse-like structures from which regulatory tyrosine phosphatases CD45 and CD148 (also known as PTPRC and PTPRJ, respectively) are excluded (Supplementary Fig. 1). The 'phagocytic synapse' now provides a model mechanism by which innate immune receptors can distinguish direct microbial contact from detection of microbes at a distance, thereby initiating direct cellular antimicrobial responses only when they are required.

Publication types

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

MeSH terms

  • Animals
  • Cell Wall / chemistry
  • Cell Wall / immunology
  • Cells, Cultured
  • Humans
  • Immunity, Innate / immunology*
  • Immunological Synapses / immunology*
  • Lectins, C-Type
  • Leukocyte Common Antigens / deficiency
  • Leukocyte Common Antigens / metabolism
  • Macrophages / immunology
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Mice
  • Models, Immunological*
  • Nerve Tissue Proteins / deficiency
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / immunology*
  • Phagocytosis / immunology*
  • Reactive Oxygen Species / metabolism
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3 / deficiency
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3 / metabolism
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / immunology
  • Signal Transduction / immunology
  • Solubility
  • beta-Glucans / chemistry
  • beta-Glucans / immunology


  • Lectins, C-Type
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Reactive Oxygen Species
  • beta-Glucans
  • dectin 1
  • Leukocyte Common Antigens
  • PTPRJ protein, human
  • Ptprj protein, mouse
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3