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- Title
Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria.
- Authors
Miao, Edward A; Leaf, Irina A; Treuting, Piper M; Mao, Dat P; Dors, Monica; Sarkar, Anasuya; Warren, Sarah E; Wewers, Mark D; Aderem, Alan
- Abstract
Macrophages mediate crucial innate immune responses via caspase-1-dependent processing and secretion of interleukin 1β (IL-1β) 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-1β 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-1β and IL-18 and establishes pyroptosis as an efficient mechanism of bacterial clearance by the innate immune system.
- Subjects
MACROPHAGES; IMMUNE response; INTERLEUKIN-1; SALMONELLA typhimurium; LABORATORY mice; NEUTROPHIL immunology; CELL death; BURKHOLDERIA
- Publication
Nature Immunology, 2010, Vol 11, Issue 12, p1136
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni.1960