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

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

Author information

1
Harvard Medical School and Division of Gastroenterology, Boston Children's Hospital, Boston, MA, USA. Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy. Unit of Cell Signalling and Innate Immunity, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
2
Harvard Medical School and Division of Gastroenterology, Boston Children's Hospital, Boston, MA, USA.
3
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
4
National Institute of Biological Sciences, Beijing 102206, China.
5
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA. Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
6
Department of Chemical and Paper Engineering, Western Michigan University, Kalamazoo, MI, USA.
7
Harvard Medical School and Division of Gastroenterology, Boston Children's Hospital, Boston, MA, USA. jonathan.kagan@childrens.harvard.edu.

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.

PMID:
27103670
PMCID:
PMC5111085
DOI:
10.1126/science.aaf3036
[Indexed for MEDLINE]
Free PMC Article

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