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.

Zanoni, I., Tan, Y., Gioia, M., Broggi, A., Ruan, J., Shi, J., et al. (2016). An endogenous caspase-11 ligand elicits interleukin-1 release from living dendritic cells. SCIENCE, 352(6290), 1232-1236 [10.1126/science.aaf3036].

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

ZANONI, IVAN
Primo
;
BROGGI, ACHILLE;
2016

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.
Si
Articolo in rivista - Articolo scientifico
Scientifica
Animals; Carrier Proteins; Caspases; Cell Death; Dendritic Cells; Immunity, Innate; Inflammasomes; Interleukin-1beta; Lipopolysaccharides; Mice; Mice, Knockout; Phospholipids; Receptors, Pattern Recognition; Toll-Like Receptor 4; Adaptive Immunity; Multidisciplinary; Medicine (all)
English
1232
1236
5
Zanoni, I., Tan, Y., Gioia, M., Broggi, A., Ruan, J., Shi, J., et al. (2016). An endogenous caspase-11 ligand elicits interleukin-1 release from living dendritic cells. SCIENCE, 352(6290), 1232-1236 [10.1126/science.aaf3036].
Zanoni, I; Tan, Y; Gioia, M; Broggi, A; Ruan, J; Shi, J; Donado, C; Shao, F; Wu, H; Springstead, J; Kagan, J
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/134605
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