Publication Date:
2016-04-23
Description:
Dendritic cells (DCs) utilize pattern recognition receptors to detect microorganisms and activate protective immunity. These cells and receptors are thought to operate in an all-or-none 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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zanoni, Ivan -- Tan, Yunhao -- Di Gioia, Marco -- Broggi, Achille -- Ruan, Jianbin -- Shi, Jianjin -- Donado, Carlos A -- Shao, Feng -- Wu, Hao -- Springstead, James R -- Kagan, Jonathan C -- New York, N.Y. -- Science. 2016 Apr 21. pii: aaf3036.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Harvard Medical School and Division of Gastroenterology, Boston Children's Hospital, Boston, Massachusetts, 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. ; Harvard Medical School and Division of Gastroenterology, Boston Children's Hospital, Boston, Massachusetts, USA. ; 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. ; National Institute of Biological Sciences, Beijing 102206, China. ; Department of Chemical and Paper Engineering, Western Michigan University, Kalamazoo, Michigan, USA. ; Harvard Medical School and Division of Gastroenterology, Boston Children's Hospital, Boston, Massachusetts, USA. jonathan.kagan@childrens.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27103670" target="_blank"〉PubMed〈/a〉
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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