An endogenous caspase-11 ligand elicits interleukin-1 release from living dendritic cells

Science. 2016 Jun 3;352(6290):1232-6. doi: 10.1126/science.aaf3036. Epub 2016 Apr 21.

Abstract

Dendritic cells (DCs) use pattern recognition receptors to detect microorganisms and activate protective immunity. These cells and receptors are thought to operate in an all-or-nothing manner, existing in an immunologically active or inactive state. Here, we report that encounters with microbial products and self-encoded oxidized phospholipids (oxPAPC) induce an enhanced DC activation state, which we call "hyperactive." Hyperactive DCs induce potent adaptive immune responses and are elicited by caspase-11, an enzyme that binds oxPAPC and bacterial lipopolysaccharide (LPS). oxPAPC and LPS bind caspase-11 via distinct domains and elicit different inflammasome-dependent activities. Both lipids induce caspase-11-dependent interleukin-1 release, but only LPS induces pyroptosis. The cells and receptors of the innate immune system can therefore achieve different activation states, which may permit context-dependent responses to infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity*
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Caspases / genetics
  • Caspases / immunology*
  • Cell Death / immunology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Immunity, Innate
  • Inflammasomes / immunology
  • Interleukin-1beta / metabolism*
  • Lipopolysaccharides / immunology*
  • Mice
  • Mice, Knockout
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Phospholipids / metabolism*
  • Receptors, Pattern Recognition / genetics
  • Receptors, Pattern Recognition / immunology*
  • Toll-Like Receptor 4 / agonists
  • Toll-Like Receptor 4 / metabolism

Substances

  • Carrier Proteins
  • Inflammasomes
  • Interleukin-1beta
  • Lipopolysaccharides
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Phospholipids
  • Receptors, Pattern Recognition
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Casp4 protein, mouse
  • Caspases