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Molecular Mechanisms of Mast Cell Activation by Cholesterol-Dependent Cytolysins
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SYSNO ASEP 0544808 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Molecular Mechanisms of Mast Cell Activation by Cholesterol-Dependent Cytolysins Author(s) Dráberová, Lubica (UMG-J) RID
Tůmová, Magda (UMG-J)
Dráber, Petr (UMG-J) RIDNumber of authors 3 Article number 670205 Source Title Frontiers in Immunology. - : Frontiers Media - ISSN 1664-3224
Roč. 12, June (2021)Number of pages 15 s. Publication form Online - E Language eng - English Country CH - Switzerland Keywords mast cell ; cholesterol-dependent cytolysins ; pore-forming toxins ; Ca2+ signaling ; cytokine production ; streptolysin O ; pneumolysin ; listeriolysin O Subject RIV EB - Genetics ; Molecular Biology OECD category Immunology R&D Projects GA18-18521S GA ČR - Czech Science Foundation (CSF) GA20-16481S GA ČR - Czech Science Foundation (CSF) Method of publishing Open access Institutional support UMG-J - RVO:68378050 UT WOS 000670070600001 DOI 10.3389/fimmu.2021.670205 Annotation Mast cells are potent immune sensors of the tissue microenvironment. Within seconds of activation, they release various preformed biologically active products and initiate the process of de novo synthesis of cytokines, chemokines, and other inflammatory mediators. This process is regulated at multiple levels. Besides the extensively studied IgE and IgG receptors, toll-like receptors, MRGPR, and other protein receptor signaling pathways, there is a critical activation pathway based on cholesterol-dependent, pore-forming cytolytic exotoxins produced by Gram-positive bacterial pathogens. This pathway is initiated by binding the exotoxins to the cholesterol-rich membrane, followed by their dimerization, multimerization, pre-pore formation, and pore formation. At low sublytic concentrations, the exotoxins induce mast cell activation, including degranulation, intracellular calcium concentration changes, and transcriptional activation, resulting in production of cytokines and other inflammatory mediators. Higher toxin concentrations lead to cell death. Similar activation events are observed when mast cells are exposed to sublytic concentrations of saponins or some other compounds interfering with the membrane integrity. We review the molecular mechanisms of mast cell activation by pore-forming bacterial exotoxins, and other compounds inducing cholesterol-dependent plasma membrane perturbations. We discuss the importance of these signaling pathways in innate and acquired immunity. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2022 Electronic address https://www.frontiersin.org/articles/10.3389/fimmu.2021.670205/full
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