Molecular Mechanisms of Mast Cell Activation by Cholesterol-Dependent Cytolysins

0544808 - ÚMG 2022 RIV CH eng J - Journal Article
Dráberová, Lubica - Tůmová, Magda - Dráber, Petr
Molecular Mechanisms of Mast Cell Activation by Cholesterol-Dependent Cytolysins.
Frontiers in Immunology. Roč. 12, June (2021), č. článku 670205. ISSN 1664-3224. E-ISSN 1664-3224
R&D Projects: GA ČR GA18-18521S; GA ČR GA20-16481S
Institutional support: RVO:68378050
Keywords : mast cell * cholesterol-dependent cytolysins * pore-forming toxins * Ca2+ signaling * cytokine production * streptolysin O * pneumolysin * listeriolysin O
OECD category: Immunology
Impact factor: 8.787, year: 2021
Method of publishing: Open access
https://www.frontiersin.org/articles/10.3389/fimmu.2021.670205/full

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.
Permanent Link: http://hdl.handle.net/11104/0321616