A Critical Role for Hemolysins and Bacterial Lipoproteins in <i>Staphylococcus aureus</i>-Induced Activation of the Nlrp3 Inflammasome
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- Raúl Muñoz-Planillo
- *Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109; and
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- Luigi Franchi
- *Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109; and
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- Lloyd S. Miller
- †Division of Dermatology, University of California, Los Angeles, CA 90095
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- Gabriel Núñez
- *Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109; and
抄録
<jats:title>Abstract</jats:title> <jats:p>The mechanism by which bacterial pathogens activate caspase-1 via Nlrp3 remains poorly understood. In this study, we show that the ability of Staphylococcus aureus, a leading cause of infection in humans, to activate caspase-1 and induce IL-1β secretion resides in culture supernatants of growing bacteria. Caspase-1 activation induced by S. aureus required α-, β-, and γ-hemolysins and the host Nlrp3 inflammasome. Mechanistically, α- and β-hemolysins alone did not trigger caspase-1 activation, but they did so in the presence of bacterial lipoproteins released by S. aureus. Notably, caspase-1 activation induced by S. aureus supernatant was independent of the P2X7 receptor and the essential TLR adaptors MyD88 and TIR domain-containing adapter-inducing IFN-β, but was inhibited by extracellular K+. These results indicate that S. aureus hemolysins circumvent the requirement of ATP and the P2X7 receptor to induce caspase-1 activation via Nlrp3. Furthermore, these studies revealed that hemolysins promote in the presence of lipoproteins the activation of the Nlrp3 inflammasome.</jats:p>
収録刊行物
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- The Journal of Immunology
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The Journal of Immunology 183 (6), 3942-3948, 2009-09-15
The American Association of Immunologists