Serglycin-independent Release of Active Mast Cell Proteases in Response to Toxoplasma gondii Infection

Sawesi, Osama; Spillmann, Dorothe; Lundén, Anna; Wernersson, Sara; Åbrink, Magnus

doi:10.1074/jbc.m110.118471

Cited by 11 publications

(14 citation statements)

References 44 publications

(56 reference statements)

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“…Although mast cells incubated with non-opsonized tachyzoites did not show any sign of degranulation, in line with previous data 51 , opsonized tachyzoites induced a strong and polarized degranulation. Interestingly, exposure of parasite to mast cell granules upon synaptic contacts was accompanied by its death, which was at least partially dependent of a functional mast cell tryptase.…”

Section: Discussionsupporting

confidence: 92%

Mast cells form antibody-dependent degranulatory synapse for dedicated secretion and defence

et al. 2015

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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.

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Section: Discussionsupporting

confidence: 92%

Mast cells form antibody-dependent degranulatory synapse for dedicated secretion and defence

et al. 2015

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“…In addition, several reports show that serglycin (or purified heparin) can enhance the actual activity of the MC proteases, either by promoting protease assembly (Hallgren et al , 2004 ) or by facilitating MC protease-catalyzed cleavage of certain substrates (Pejler and Sadler , 1999 ;. However, the release of MC proteases may occur independently of serglycin proteoglycan, at least during an in vivo response to parasite infection (Sawesi et al , 2010 ).…”

Section: Introductionmentioning

confidence: 99%

Mast cells limit extracellular levels of IL-13 via a serglycin proteoglycan-serine protease axis

Waern

Karlsson

Thorpe

et al. 2012

Biological Chemistry

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: Mast cell (MC) granules contain large amounts of proteases of the chymase, tryptase and carboxypeptidase A (MC-CPA) type that are stored in complex with serglycin, a proteoglycan with heparin side chains. Hence, serglycinprotease complexes are released upon MC degranulation and may influence local inflammation. Here we explored the possibility that a serglycin-protease axis may regulate levels of IL-13, a cytokine involved in allergic asthma. Indeed, we found that wild-type MCs efficiently degraded exogenous or endogenously produced IL-13 upon degranulation, whereas serglycin −/− MCs completely lacked this ability. Moreover, MC-mediated IL-13 degradation was blocked both by a serine protease inhibitor and by a heparin antagonist, which suggests that IL-13 degradation is catalyzed by serglycin-dependent serine proteases and that optimal IL-13 degradation is dependent on both the serglycin and the protease component of the serglycin-protease complex. Moreover, IL-13 degradation was abrogated in MC-CPA −/− MC cultures, but was normal in cultures of MCs with an inactivating mutation of MC-CPA, which suggests that the IL-13-degrading serine proteases rely on MC-CPA protein. Together, our data implicate a serglycin-serine protease axis in the regulation of extracellular levels of IL-13. Reduction of IL-13 levels through this mechanism possibly can provide a protective function in the context of allergic inflammation.

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“…The use of MC-deficient Kit W / Kit W-v mice demonstrated that the influx of Ly6G + cells toward the peritoneal cavity was significantly reduced compared to control littermates, indicating that MCs are an important chemokine source driving PMN recruitment to the peritoneal cavity during T. gondii infection (43). In both wild-type and serglycin-deficient mice, intraperitoneal infection with T. gondii resulted in highly increased extracellular levels of glycosaminoglycans, including hyaluronan and chondroitin sulfate A, suggesting that serglycin proteoglycan is dispensable for normal secretion and activity of MC proteases in response to T. gondii infection (81). A murine model showed that infection of T. gondii increased not only the number of MCs at the site of infection but also a noticeable degree of MC degranulation.…”

Section: Mcs In T Gondii Infectionmentioning

confidence: 99%

The Roles of Mast Cells in Parasitic Protozoan Infections

Huang

2017

Front. Immunol.

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Protozoan parasites such as Plasmodium spp., Leishmania spp., Trypanosoma spp., and Toxoplasma gondii are major causes of parasitic diseases in both humans and animals. The immune system plays a critical role against protozoa, but their immune mechanism remains poorly understood. This highlights the need to investigate the function of immune cells involved in the process of parasite infections and the responses of host immune system to parasite infections. Mast cells (MCs) are known to be central players in allergy and anaphylaxis, and it has been demonstrated that MCs have crucial roles in host defense against a number of different pathogens, including parasites. To date, there are many studies that have examined the interaction of helminth-derived antigens and MCs. As one of the major effector cells, MCs also play an important role in the immune response against some parasitic protozoa, but their role in protozoan infections is, however, less well characterized. Herein, we review the current knowledge about the roles of MCs and their mediators during infections involving highly pathogenic protozoa including Plasmodium spp., Leishmania spp., Trypanosoma spp., and T. gondii. We offer a general review of the data from patients and experimental animal models infected with the aforementioned protozoa, which correlate MCs and MC-derived mediators with exacerbated inflammation and disease progression as well as protection against the parasitic infections in different circumstances. This review updates our current understanding of the roles of MCs during parasitic protozoan infections, and the participation of MCs in parasitic protozoan infections could be of a potential therapeutic target.

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Serglycin-independent Release of Active Mast Cell Proteases in Response to Toxoplasma gondii Infection

Cited by 11 publications

References 44 publications

Mast cells form antibody-dependent degranulatory synapse for dedicated secretion and defence

Mast cells form antibody-dependent degranulatory synapse for dedicated secretion and defence

Mast cells limit extracellular levels of IL-13 via a serglycin proteoglycan-serine protease axis

The Roles of Mast Cells in Parasitic Protozoan Infections

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