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.

Imaging protective mast cells in living mice during severe contact hypersensitivity

“…injection of the probe, and such fluorescent signal stayed bright and stable for at least 120 days after injection in resting mice (no later time points were investigated) (Supplemental Figure 1B). This long-term storage of the dye in MC granules is likely due to the presence in the granules of high levels of negatively charged proteoglycans (e.g., heparin), to which avidin can strongly bind (18,23,24), as well as to the low pH of MC granules, which might protect the avidin probe from protease-mediated degradation (25). Taken together, these results demonstrate that a single i.d.…”

“…injection of fluorochrome-labeled avidin (sulforhodamine 101-coupled avidin [Av.SRho]) into the ear pinna dermis 10 to 30 minutes before performing 2-photon microscopy (15). During MC degranulation, which results in fusion of secretory granule membranes with the plasma membrane (16,17), externalized granule matrices are rapidly bound by soluble fluorescent Av.SRho probe present in the microenvironment, allowing imaging by high-resolution confocal and in vivo 2-photon microscopy of such exteriorized granule structures (15,18). While this method is useful for identifying exteriorized MC granule structures, it requires (a) that MCs are activated to degranulate, and (b) using specific MC reporter mice (e.g., Mcpt5-EYFP mice; see refs.…”

Functional role of kynurenine and aryl hydrocarbon receptor axis in chronic rhinosinusitis with nasal polyps

“…We first investigated the spatiotemporal dynamics of mast cell degranulation by using a soluble fluorochrome-labeled avidin (sulforhodamine 101–coupled avidin [Av.SRho]). 47,48 OVA-sensitized BMMCs were challenged with OVA (10 μg/mL) in the presence of Av.SRho and inspected by time-lapse confocal microscopy. As shown in Fig 4, H , this stimulation induced granule budding on the BMMCs.…”

Mast-Cell-Derived TNF Amplifies CD8+ Dendritic Cell Functionality and CD8+ T Cell Priming

“…Moreover, the distinct effect of MC-TNF may result from its embedding and stabilization within the heparin core of released MC granules. Recently, Joulia et al (2015) prove MCs to form degranulatory synapses with target cells inducing a polarized exocytosis of their granules. Given the hapten-induced MC degranulation, this way of communication may explain the distinct effect of MC-derived TNF despite the simultaneous release of soluble TNF by other skin-resident cells.…”