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

Raúl Muñoz-Planillo, Luigi Franchi, Lloyd S. Miller, Gabriel Núñez

Research output: Contribution to journalArticlepeer-review

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-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.

Original languageEnglish (US)
Pages (from-to)3942-3948
Number of pages7
JournalJournal of Immunology
Volume183
Issue number6
DOIs
StatePublished - Sep 15 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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