title: Inflammation. Neutrophil extracellular traps license macrophages for cytokine production in atherosclerosis.
abstract: 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.
authors.affiliation: Mill Hill Laboratory, Francis Crick Institute, London NW7 1AA, UK.
authors.forename: Annika
authors.initials: A
authors.lastname: Warnatsch
authors.affiliation: Mill Hill Laboratory, Francis Crick Institute, London NW7 1AA, UK.
authors.forename: Marianna
authors.initials: M
authors.lastname: Ioannou
authors.affiliation: Mill Hill Laboratory, Francis Crick Institute, London NW7 1AA, UK.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Mill Hill Laboratory, Francis Crick Institute, London NW7 1AA, UK. veni.p@crick.ac.uk.
authors.forename: Venizelos
authors.initials: V
authors.lastname: Papayannopoulos
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000276:immunology*; D002478:Cells, Cultured; D002784:Cholesterol / Q000737:chemistry / Q000276:immunology; D004195:Disease Models, Animal; D065206:Extracellular Traps / Q000276:immunology*; D006801:Humans; D058847:Inflammasomes / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D053583:Interleukin-1beta / Q000096:biosynthesis* / Q000235:genetics; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D009504:Neutrophils / Q000276:immunology*; D015398:Signal Transduction; D058504:Th17 Cells / Q000276:immunology; D014158:Transcription, Genetic
chemical_list: D001057:Apolipoproteins E; D058847:Inflammasomes; D053583:Interleukin-1beta; D002784:Cholesterol