title: Activation of the innate immune receptor Dectin-1 upon formation of a 'phagocytic synapse'.
abstract: 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.
authors.affiliation: IBD and Immunobiology Research Institute, 8700 Beverly Boulevard, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
authors.forename: Helen S
authors.initials: HS
authors.lastname: Goodridge
authors.forename: Christopher N
authors.initials: CN
authors.lastname: Reyes
authors.forename: Courtney A
authors.initials: CA
authors.lastname: Becker
authors.forename: Tamiko R
authors.initials: TR
authors.lastname: Katsumoto
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Wolf
authors.forename: Nandita
authors.initials: N
authors.lastname: Bose
authors.forename: Anissa S H
authors.initials: AS
authors.lastname: Chan
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Magee
authors.forename: Michael E
authors.initials: ME
authors.lastname: Danielson
authors.forename: Arthur
authors.initials: A
authors.lastname: Weiss
authors.forename: John P
authors.initials: JP
authors.lastname: Vasilakos
authors.forename: David M
authors.initials: DM
authors.lastname: Underhill
mesh_terms: D000818:Animals; D002473:Cell Wall / Q000737:chemistry / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D054992:Immunological Synapses / Q000276:immunology*; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens / Q000172:deficiency / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018448:Models, Immunological; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000172:deficiency / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D012995:Solubility; D047071:beta-Glucans / Q000737:chemistry / Q000276:immunology; D000099181:Dectin-1
chemical_list: D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D017382:Reactive Oxygen Species; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3; D047071:beta-Glucans; D000099181:Dectin-1; C486288:PTPRJ protein, human; C098066:Ptprj protein, mouse