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

ABSTRACT: Staphylococcus aureus is a dangerous pathogen that can cause necrotizing infections characterized by massive inflammatory responses and tissue destruction. Staphylococcal ?-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-1? and programmed necrotic cell death. We sought to determine the role of ?-hemolysin-mediated activation of NLRP3 in the pathogenesis of S. aureus pneumonia. We show that ?-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 ?-hemolysin or live S. aureus is independent of interleukin-1? 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.

SUBMITTER: Kebaier C 

PROVIDER: S-EPMC3274379 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature