Membrane Cholesterol Is Crucial for Clostridium difficile Surface Layer Protein Binding and Triggering Inflammasome Activation.
FRONTIERS IN IMMUNOLOGY(2020)
摘要
Clostridium difficile, an obligate anaerobic gram-positive bacillus, generates spores and is commonly found colonizing the human gut. Patients withC. difficileinfection (CDI) often exhibit clinical manifestations of pseudomembranous colitis or antibiotic-associated diarrhea. Surface layer proteins (SLPs) are the most abundant proteins in theC. difficilecell wall, suggesting that they might involve in immune recognition. Our previous results demonstrated thatC. difficiletriggers inflammasome activation. Here, we found SLPs as well asC. difficileinduced inflammasome activation, and in a dose-dependent manner. In addition, the cholesterol-rich microdomains on the cell membrane (also referred to as lipid rafts) are thought to be crucial for bacterial adhesion and signal transduction. We demonstrated that lipid rafts participated inC. difficileSLPs binding to the cell membrane. Fluorescence microscopy showed that membrane cholesterol depletion by methyl-beta-cyclodextrin (M beta CD) reduced the association of SLPs with the cell surface. The coalescence of SLPs in the cholesterol-rich microdomains was confirmed inC. difficile-infected cells. Furthermore, the inflammasome activations induced by SLPs orC. difficilewere abrogated by M beta CD. Our results demonstrate that SLPs recruit the lipid rafts, which may be a key step forC. difficilecolonization and inducing inflammasome activation.
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关键词
Clostridium difficile,membrane cholesterol,lipid rafts,surface layer proteins,inflammasome activation
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