Science · 2016 · 567 citations · 22 references
Life SciencesImmunologyMicrobiologyAdaptive ImmunityInflammationInnate ImmunityCaspase ActivationDendritic Cell BiologyImmune Cell SignalingInflammatory Cell ResponsesInflammatory SignalingInnate Immune ResponseBacterial Lipopolysaccharide RecognitionCaspase SignalingCaspase-mediated Inflammatory SignalingCell Death In ImmunityContext-dependent SignalingDendritic Cell Inflammatory ResponsesDendritic Cell Innate SensingOxidized Phospholipids
Dendritic cells initiate protective immunity by binding molecules derived from microbes or dying cells. The study examined how microbial and endogenous signals interact to shape the ensuing immune response. Oxidized phospholipid oxPAPC binds caspase‑11 in dendritic cells, triggering IL‑1 release and strong adaptive immunity without cell death, whereas co‑binding with bacterial LPS induces IL‑1 production and cell death, demonstrating that context‑dependent signals modulate the immune response. Zanoni et al., Science, this issue p.
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
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