Staphylococcus aureus α-Hemolysin Mediates Virulence in a Murine Model of Severe Pneumonia Through Activation of the NLRP3 Inflammasome
Staphylococcus aureus α-Hemolysin Mediates Virulence in a Murine Model of Severe Pneumonia Through Activation of the NLRP3 Inflammasome
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DOI：
10.1093/infdis/jir846
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发表时间：
2012-03-01
影响因子：
6.4
通讯作者：
Duncan, Joseph A.
中科院分区：
文献类型：
--
作者：
Kebaier, Chahnaz;Chamberland, Robin R.;Duncan, Joseph A.
金黄色葡萄球菌是一种危险的病原体，可引起坏死性感染，其特征在于大量炎症反应和组织破坏。葡萄球菌α-溶血素是重症葡萄球菌的重要毒力因子。金黄色肺炎它激活核苷酸结合结构域和富含亮氨酸重复序列的基因家族，pyrin结构域3（NLRP 3）炎性体，诱导白细胞介素-1 β的产生和程序性坏死细胞死亡。我们试图确定α-溶血素介导的NLRP 3激活在S.金黄色肺炎我们发现α-溶血素在S.金黄色葡萄球菌肺炎，诱导坏死性肺损伤。此外，Nlrp 3（-/-）小鼠的肺炎不太严重。分离的α-溶血素或活的S.金黄色葡萄球菌的坏死不依赖于白细胞介素-1 β信号传导，表明NLRP 3诱导的坏死在严重感染的发病机制中起作用。这项工作证明了宿主炎症信号的剥削，由S。并表明NLRP 3炎性体是严重金黄色葡萄球菌药物干预的潜在靶点。金黄色葡萄球菌感染。
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.