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

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  • Miao, Edward A.
    • Other Affiliation: Institute for Systems Biology, Seattle, Washington, USA
  • Leaf, Irina A.
    • Other Affiliation: Institute for Systems Biology, Seattle, Washington, USA
  • Treuting, Piper M.
    • Other Affiliation: Department of Comparative Medicine, University of Washington, Seattle, Washington, USA
  • Mao, Dat P.
    • Other Affiliation: Institute for Systems Biology, Seattle, Washington, USA
  • Dors, Monica
    • Other Affiliation: Institute for Systems Biology, Seattle, Washington, USA
  • Sarkar, Anasuya
    • Other Affiliation: Pulmonary, Critical Care, Allergy and Sleep Medicine, The Dorothy M. Davis Heart and Lung Research Institute, Ohio State University, Columbus, Ohio, USA
  • Warren, Sarah E.
    • Other Affiliation: Institute for Systems Biology, Seattle, Washington, USA; Department of Immunology, University of Washington, Seattle, Washington, USA.
  • Wewers, Mark D.
    • Other Affiliation: Pulmonary, Critical Care, Allergy and Sleep Medicine, The Dorothy M. Davis Heart and Lung Research Institute, Ohio State University, Columbus, Ohio, USA
  • Aderem, Alan
    • Other Affiliation: Institute for Systems Biology, Seattle, Washington, USA
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.
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  • Article
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  • In Copyright
Journal title
  • Nature Immunology
Journal volume
  • 11
Journal issue
  • 12
Page start
  • 1136
Page end
  • 1142
Language
  • English
Version
  • Postprint
ISSN
  • 1529-2916

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