title: Mast cells form antibody-dependent degranulatory synapse for dedicated secretion and defence.
abstract: 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.
authors: Inserm, U1043, Toulouse F-31300, France; Université de Toulouse, UPS, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse F-31300, France.
authors: Régis
authors: R
authors: Joulia
authors: Inserm, U1043, Toulouse F-31300, France; Université de Toulouse, UPS, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse F-31300, France.
authors: Nicolas
authors: N
authors: Gaudenzio
authors: Inserm, U1043, Toulouse F-31300, France; Université de Toulouse, UPS, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse F-31300, France.
authors: Magda
authors: M
authors: Rodrigues
authors: Inserm, U1043, Toulouse F-31300, France; Université de Toulouse, UPS, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse F-31300, France.
authors: Jodie
authors: J
authors: Lopez
authors: Inserm, U1043, Toulouse F-31300, France; Université de Toulouse, UPS, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse F-31300, France.
authors: Nicolas
authors: N
authors: Blanchard
authors: Inserm, U1043, Toulouse F-31300, France; Université de Toulouse, UPS, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse F-31300, France.
authors: Salvatore
authors: S
authors: Valitutti
authors: Inserm, U1043, Toulouse F-31300, France; Université de Toulouse, UPS, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse F-31300, France.
authors: Eric
authors: E
authors: Espinosa
mesh_terms: D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016923:Cell Death / Q000187:drug effects; D015550:Cell Degranulation / Q000187:drug effects / Q000276:immunology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D016764:Cell Polarity / Q000187:drug effects; D018925:Chemokines / Q000096:biosynthesis; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D054992:Immunological Synapses / Q000187:drug effects / Q000378:metabolism*; D008024:Ligands; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D009895:Opsonin Proteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017455:Receptors, IgE / Q000378:metabolism; D000069283:Rituximab / Q000494:pharmacology; D014122:Toxoplasma / Q000187:drug effects / Q000502:physiology
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D018925:Chemokines; C110810:LAT protein, human; D008024:Ligands; D008565:Membrane Proteins; D009895:Opsonin Proteins; D017455:Receptors, IgE; D007073:Immunoglobulin E; D000069283:Rituximab