Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria.

ABSTRACT: Macrophages mediate crucial innate immune responses via caspase-1-dependent processing and secretion of interleukin 1? (IL-1?) 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? 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? and IL-18 and establishes pyroptosis as an efficient mechanism of bacterial clearance by the innate immune system.

SUBMITTER: Miao EA 

PROVIDER: S-EPMC3058225 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature