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

Full 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.

Author information

Author/s: Muñoz-Planillo, Raúl (R); Franchi, Luigi (L); Miller, Lloyd S (LS); Núñez, Gabriel (G);

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

Grants: AI063331 (Agency:NIAID NIH HHS) ; AI064748 (Agency:NIAID NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol), published in United States. (Language: eng)

Reference: 2009-Sep; vol 183 (issue 6) : pp 3942-8

Dates: Created 2009/09/03; Completed 2009/09/23; Revised 2009/10/19;

PMID: 19717510, status: MEDLINE (last retrieved date: 10/20/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Bacterial Proteins (0) ; CIAS1 protein, mouse (0) ; Carrier Proteins (0) ; Hemolysin Proteins (0) ; Interleukin-1beta (0) ; Lipoproteins (0) ; Multiprotein Complexes (0) ; Receptors, Purinergic P2 (0) ; purinoceptor P2Z (0) ; Adenosine Triphosphate (56-65-5) ; Potassium (7440-09-7) ; Caspase 1 (EC 3.4.22.36)

These are the most related articles currently in our database: