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.
Highlights
Mast cells are tissue-resident immune cells that play a key role in inflammation and allergy
To define the spatiotemporal characteristics of mast cell degranulation, we set-up a method to monitor, in live cells, the early steps of granule exocytosis using fluorochrome-labelled avidin, a probe that binds heparin contained in mast cell granules[34]
Part of the exocyted granules were released in the culture medium, a substantial part of granule content was retained on the Human mast cells (hMCs) surface (Supplementary Movie 1)
Summary
Mast cells are tissue-resident immune cells that play a key role in inflammation and allergy. 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. Unlike FceRI, FcgRIIA cannot bind to monomeric antibodies in the absence of antigen but it can bind to antibodies as multivalent immune complexes with high avidity Those receptors belong to the immunoreceptor tyrosine-based activation motif (ITAM)containing superfamily of immunoreceptors and are coupled to a signalling cascade involving src-kinases triggering, [Ca2 þ ]i increase and actin cytoskeleton remodelling[26,27,28]. We sought to monitor the spatiotemporal dynamics of mast cell degranulation following local stimulation by mean of IgG- or IgE-targeted cell surface antigens
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