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Mast cells form antibody-dependent degranulatory synapse for dedicated secretion and defence
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Journal Article
Mast cells form antibody-dependent degranulatory synapse for dedicated secretion and defence
2015
Overview
Mast cells are tissue-resident immune cells that play a key role in inflammation and allergy. Here we show that interaction of mast cells with antibody-targeted cells induces the polarized exocytosis of their granules resulting in a sustained exposure of effector enzymes, such as tryptase and chymase, at the cell-cell contact site. This previously unidentified mast cell effector mechanism, which we name the antibody-dependent degranulatory synapse (ADDS), is triggered by both IgE- and IgG-targeted cells. ADDSs take place within an area of cortical actin cytoskeleton clearance in the absence of microtubule organizing centre and Golgi apparatus repositioning towards the stimulating cell. Remarkably, IgG-mediated degranulatory synapses also occur upon contact with opsonized Toxoplasma gondii tachyzoites resulting in tryptase-dependent parasite death. Our results broaden current views of mast cell degranulation by revealing that human mast cells form degranulatory synapses with antibody-targeted cells and pathogens for dedicated secretion and defence.
Publisher
Nature Publishing Group
Subject
/ Adaptor Proteins, Signal Transducing - metabolism
/ Antibodies, Monoclonal - pharmacology
/ B-Lymphocytes - drug effects
/ Cell Degranulation - drug effects
/ Cell Degranulation - immunology
/ Cell Membrane - drug effects
/ Cell Polarity - drug effects
/ Cytoplasmic Granules - drug effects
/ Cytoplasmic Granules - metabolism
/ Humans
/ Humans Immunoglobulin E / immunology
/ Immunoglobulin E - immunology
/ Immunological Synapses - drug effects
/ Immunological Synapses - metabolism
/ Ligands
/ Membrane Proteins - metabolism
/ Molecular Dynamics Simulation
/ Opsonin Proteins - metabolism
