Journal
SCIENCE
Volume 352, Issue 6290, Pages 1232-1236Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aaf3036
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Funding
- NIH [AI093589, AI072955, P30 DK34854, 1R15HL121770-01A1, 1R01AI121066-01A1]
- Burroughs Wellcome Fund
- Harvard Digestive Diseases Center [P30 DK34854]
- Cariplo Foundation
- Jane Coffin Childs Fund
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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.
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