期刊
JOURNAL OF INFECTIOUS DISEASES
卷 205, 期 5, 页码 807-817出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jir846
关键词
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资金
- Burroughs Wellcome Fund
- National Institutes of Health [AI057157, AI088255, AI077437, HL071802, HL048160]
- University of North Carolina [T32AI007001]
Staphylococcus aureus is a dangerous pathogen that can cause necrotizing infections characterized by massive inflammatory responses and tissue destruction. Staphylococcal alpha-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 beta and programmed necrotic cell death. We sought to determine the role of alpha-hemolysin-mediated activation of NLRP3 in the pathogenesis of S. aureus pneumonia. We show that alpha-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 alpha-hemolysin or live S. aureus is independent of interleukin-1 beta 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.
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