A Critical Role for Hemolysins and Bacterial Lipoproteins in Staphylococcus aureus-Induced Activation of the Nlrp3 Inflammasome
Year: 2009
Type: article
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.
Source: The Journal of Immunology
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Awards: Role of ASC signaling Pathway in Inflammatory Disease, G4402410546, Cryopyrin/NLRP3 Signaling in Inflammation and Innate Immunity, Role of Ipaf in Inflammation and Host Defense, Cryopyrin/NLRP3 Signaling in Inflammation and Innate Immunity, Cryopyrin/NLRP3 Signaling in Inflammation and Innate Immunity
OpenAlex ID: W2127453904