Neutrophil extracellular traps license macrophages for cytokine production in atherosclerosis
journal contributionposted on 22.09.2020, 11:50 by Annika Warnatsch, Marianna Ioannou, Qian Wang, Venizelos Papayannopoulos
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.
AnimalsApolipoproteins EAtherosclerosisCells, CulturedCholesterolDisease Models, AnimalExtracellular TrapsHumansInflammasomesInflammationInterleukin-1betaMacrophagesMiceMice, Mutant StrainsNeutrophilsSignal TransductionTh17 CellsTranscription, GeneticPapayannopoulos MC_UP_1202/13General Science & Technology