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

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Science  03 Jun 2016:
Vol. 352, Issue 6290, pp. 1232-1236
DOI: 10.1126/science.aaf3036

Immune activation in context

Dendritic cells (DCs) initiate protective immunity upon binding molecules derived from microbes or released from dying cells. Zanoni et al. examined how microbial and endogenous signals interact to shape the course of the ensuing immune response (see the Perspective by Napier and Monack). They found that oxPAPC, an oxidized phospholipid released from dying cells, binds to a protein called caspase-11 in DCs, activating an inflammatory program in these cells. Whereas caspase-11 binding to oxPAPC and bacterial lipopolysaccharide causes DCs to produce the cytokine interleukin-1 (IL-1) and undergo cell death, binding to oxPAPC alone triggers DCs to secrete IL-1 and induce strong adaptive immunity. Thus, context-dependent signals can shape the ensuing immune response.

Science, this issue p. 1232; see also p. 1173


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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