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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Miao, EA; Leaf, IA; Treuting, PM; Mao, DP; Dors, M; Sarkar, A; Warren, SE; Wewers, MD; Aderem, A

Published Date

  • December 2010

Published In

Volume / Issue

  • 11 / 12

Start / End Page

  • 1136 - 1142

PubMed ID

  • 21057511

Pubmed Central ID

  • PMC3058225

Electronic International Standard Serial Number (EISSN)

  • 1529-2916

International Standard Serial Number (ISSN)

  • 1529-2908

Digital Object Identifier (DOI)

  • 10.1038/ni.1960

Language

  • eng