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J Infect Dis. 2012 Mar 1;205(5):807-17. doi: 10.1093/infdis/jir846. Epub 2012 Jan 25.

Staphylococcus aureus α-hemolysin mediates virulence in a murine model of severe pneumonia through activation of the NLRP3 inflammasome.

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1
Department of Medicine, Division of Infectious Diseases, University of North Carolina, Chapel Hill, USA.

Abstract

Staphylococcus aureus is a dangerous pathogen that can cause necrotizing infections characterized by massive inflammatory responses and tissue destruction. Staphylococcal α-hemolysin is an essential virulence factor in severe S. aureus pneumonia. It activates the nucleotide-binding domain and leucine-rich repeat containing gene family, pyrin domain containing 3 (NLRP3) inflammasome to induce production of interleukin-1β and programmed necrotic cell death. We sought to determine the role of α-hemolysin-mediated activation of NLRP3 in the pathogenesis of S. aureus pneumonia. We show that α-hemolysin activates the NLRP3 inflammasome during S. aureus pneumonia, inducing necrotic pulmonary injury. Moreover, Nlrp3(-/-) mice have less-severe pneumonia. Pulmonary injury induced by isolated α-hemolysin or live S. aureus is independent of interleukin-1β signaling, implicating NLRP3-induced necrosis in the pathogenesis of severe infection. This work demonstrates the exploitation of host inflammatory signaling by S. aureus and suggests the NLRP3 inflammasome as a potential target for pharmacologic interventions in severe S. aureus infections.

PMID:
22279123
PMCID:
PMC3274379
DOI:
10.1093/infdis/jir846
[Indexed for MEDLINE]
Free PMC Article

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