First Author | Liu T | Year | 2014 |
Journal | Cell Rep | Volume | 8 |
Issue | 4 | Pages | 974-82 |
PubMed ID | 25127135 | Mgi Jnum | J:297265 |
Mgi Id | MGI:6148093 | Doi | 10.1016/j.celrep.2014.07.012 |
Citation | Liu T, et al. (2014) Single-cell imaging of caspase-1 dynamics reveals an all-or-none inflammasome signaling response. Cell Rep 8(4):974-82 |
abstractText | Inflammasome-mediated caspase-1 activation is involved in cell death and the secretion of the proinflammatory cytokine interleukin-1beta (IL-1beta). Although the dynamics of caspase-1 activation, IL-1beta 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-1beta release demonstrated that dead macrophages containing activated caspase-1 release a local burst of IL-1beta in a digital manner, which identified these macrophages as the main source of IL-1beta within cell populations. Our results highlight the value of single-cell analysis in enhancing understanding of the inflammasome system and chronic inflammatory diseases. |