Single-cell imaging of caspase-1 dynamics reveals an all-or-none inflammasome signaling response

Ting Liu, Yoshifumi Yamaguchi, Yoshitaka Shirasaki, Koichi Shikada, Mai Yamagishi, Katsuaki Hoshino, Tsuneyasu Kaisho, Kiwamu Takemoto, Toshihiko Suzuki, Erina Kuranaga, Osamu Ohara, Masayuki Miura

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89 Citations (Scopus)

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, weconducted 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 ina digital manner, which identified these macrophages as themain 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.

Original languageEnglish
Pages (from-to)974-982
Number of pages9
JournalCell Reports
Volume8
Issue number4
DOIs
Publication statusPublished - 2014 Aug 21

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Liu, T., Yamaguchi, Y., Shirasaki, Y., Shikada, K., Yamagishi, M., Hoshino, K., Kaisho, T., Takemoto, K., Suzuki, T., Kuranaga, E., Ohara, O., & Miura, M. (2014). Single-cell imaging of caspase-1 dynamics reveals an all-or-none inflammasome signaling response. Cell Reports, 8(4), 974-982. https://doi.org/10.1016/j.celrep.2014.07.012