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

作者：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.^*

来源：Science, 2016, 352(6290): 1232-1236.

DOI：10.1126/science.aaf3036

• INFLAMMATORY CASPASES
• OXIDIZED PHOSPHOLIPIDS
• IMMUNE-SYSTEM
• DANGER
• ACTIVATION
• PROTECTS
• FAMILY
• DEATH
• LPS

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.

• 出版日期2016-6-3
• 单位北京生命科学研究所