Journal
JOURNAL OF IMMUNOLOGY
Volume 183, Issue 6, Pages 3942-3948Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0900729
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Funding
- Fulbright-Ramon Areces Fellowship [AI063331, AI064748]
- Arthritis Foundation
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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-1 beta secretion resides in culture supernatants of growing bacteria. Caspase-1 activation induced by S. aureus required alpha-, beta-, and gamma-hemolysins and the host Nlrp3 inflammasome. Mechanistically, alpha- and beta-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-beta, 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. The Journal of Immunology, 2009, 183: 3942-3948.
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