期刊
NATURE IMMUNOLOGY
卷 11, 期 12, 页码 1136-U94出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.1960
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资金
- US National Institutes of Health [U54 AI057141, AI052286]
Macrophages mediate crucial innate immune responses via caspase-1-dependent processing and secretion of interleukin 1 beta (IL-1 beta) and IL-18. Although infection with wild-type Salmonella typhimurium is lethal to mice, we show here that a strain that persistently expresses flagellin was cleared by the cytosolic flagellin-detection pathway through the activation of caspase-1 by the NLRC4 inflammasome; however, this clearance was independent of IL-1 beta and IL-18. Instead, caspase-1-induced pyroptotic cell death released bacteria from macrophages and exposed the bacteria to uptake and killing by reactive oxygen species in neutrophils. Similarly, activation of caspase-1 cleared unmanipulated Legionella pneumophila and Burkholderia thailandensis by cytokine-independent mechanisms. This demonstrates that activation of caspase-1 clears intracellular bacteria in vivo independently of IL-1 beta and IL-18 and establishes pyroptosis as an efficient mechanism of bacterial clearance by the innate immune system.
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