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J Immunol. 2009 Sep 15;183(6):3942-8. doi: 10.4049/jimmunol.0900729. Epub 2009 Aug 28.

A critical role for hemolysins and bacterial lipoproteins in Staphylococcus aureus-induced activation of the Nlrp3 inflammasome.

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  • 1Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

Abstract

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-1beta 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.

PMID:
19717510
[PubMed - indexed for MEDLINE]
PMCID:
PMC2762867
Free PMC Article
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