An endogenous caspase-11 ligand elicits interleukin-1 release from living dendritic cells
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:
-
Science
- Pub Date:
- June 2016
- DOI:
- 10.1126/science.aaf3036
- Bibcode:
- 2016Sci...352.1232Z
- Keywords:
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- IMMUNOLOGY