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

Ivan ZanoniDepartment of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, ItalyYunhao TanHarvard Medical School and Division of Gastroenterology, Boston Children’s Hospital, Boston, MA, USAMarco Di GioiaHarvard Medical School and Division of Gastroenterology, Boston Children’s Hospital, Boston, MA, USAAchille BroggiHarvard Medical School and Division of Gastroenterology, Boston Children’s Hospital, Boston, MA, USAJianbin RuanDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USAJianjin ShiNational Institute of Biological Sciences, Beijing 102206, ChinaCarlos DonadoHarvard Medical School and Division of Gastroenterology, Boston Children’s Hospital, Boston, MA, USAFeng ShaoNational Institute of Biological Sciences, Beijing 102206, ChinaHao WuDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USAJames R. SpringsteadDepartment of Chemical and Paper Engineering, Western Michigan University, Kalamazoo, MI, USAJonathan C. KaganHarvard Medical School and Division of Gastroenterology, Boston Children’s Hospital, Boston, MA, USA

2016en

ABI

Annotatsiya

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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Identifikatorlar

DOI: 10.1126/science.aaf3036

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