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Neutrophil extracellular traps license macrophages for cytokine production in atherosclerosis

Annika WarnatschMill Hill Laboratory, Francis Crick Institute, London NW7 1AA, UKΜαριάννα ΙωάννουMill Hill Laboratory, Francis Crick Institute, London NW7 1AA, UKQian WangMill Hill Laboratory, Francis Crick Institute, London NW7 1AA, UKVenizelos PapayannopoulosMill Hill Laboratory, Francis Crick Institute, London NW7 1AA, UK

2015en

ABI

Annotatsiya

Secretion of the cytokine interleukin-1β (IL-1β) by macrophages, a major driver of pathogenesis in atherosclerosis, requires two steps: Priming signals promote transcription of immature IL-1β, and then endogenous "danger" signals activate innate immune signaling complexes called inflammasomes to process IL-1β for secretion. Although cholesterol crystals are known to act as danger signals in atherosclerosis, what primes IL-1β transcription remains elusive. Using a murine model of atherosclerosis, we found that cholesterol crystals acted both as priming and danger signals for IL-1β production. Cholesterol crystals triggered neutrophils to release neutrophil extracellular traps (NETs). NETs primed macrophages for cytokine release, activating T helper 17 (TH17) cells that amplify immune cell recruitment in atherosclerotic plaques. Therefore, danger signals may drive sterile inflammation, such as that seen in atherosclerosis, through their interactions with neutrophils.

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DOI: 10.1126/science.aaa8064

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