RRC ID 31341
Author Liu T, Yamaguchi Y, Shirasaki Y, Shikada K, Yamagishi M, Hoshino K, Kaisho T, Takemoto K, Suzuki T, Kuranaga E, Ohara O, Miura M.
Title Single-cell imaging of caspase-1 dynamics reveals an all-or-none inflammasome signaling response.
Journal Cell Rep
Abstract Inflammasome-mediated caspase-1 activation is involved in cell death and the secretion of the proinflammatory cytokine interleukin-1β (IL-1β). Although the dynamics of caspase-1 activation, IL-1β secretion, and cell death have been examined with bulk assays in population-level studies, they remain poorly understood at the single-cell level. In this study, we conducted single-cell imaging using a genetic fluorescence resonance energy transfer sensor that detects caspase-1 activation. We determined that caspase-1 exhibits all-or-none (digital) activation at the single-cell level, with similar activation kinetics irrespective of the type of inflammasome or the intensity of the stimulus. Real-time concurrent detection of caspase-1 activation and IL-1β release demonstrated that dead macrophages containing activated caspase-1 release a local burst of IL-1β in a digital manner, which identified these macrophages as the main source of IL-1β within cell populations. Our results highlight the value of single-cell analysis in enhancing understanding of the inflammasome system and chronic inflammatory diseases.
Volume 8(4)
Pages 974-82
Published 2014-8-21
DOI 10.1016/j.celrep.2014.07.012
PII S2211-1247(14)00579-8
PMID 25127135
MeSH Animals Caspase 1 / physiology* Cells, Cultured Enzyme Activation Humans Inflammasomes / metabolism* Interleukin-1beta / physiology Kinetics Lipopolysaccharides / pharmacology Macrophages, Peritoneal / enzymology Macrophages, Peritoneal / immunology Mice, Transgenic Signal Transduction Single-Cell Analysis
IF 8.109
Times Cited 81
Mice RBRC01828