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Cell Rep. 2014 Aug 21;8(4):974-82. doi: 10.1016/j.celrep.2014.07.012. Epub 2014 Aug 7.

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

Author information

1
Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
2
Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan; PRESTO, Japan Science and Technology Agency, Chiyoda-ku, Tokyo 102-0076, Japan. Electronic address: bunbun@mol.f.u-tokyo.ac.jp.
3
Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan.
4
Department of Immunology, Faculty of Medicine, Kagawa University, Kita-gun, Kagawa 761-0793, Japan; Laboratory for Immune Regulation, World Premier International Research Center Initiative Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0861, Japan; Laboratory for Host Defense, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan.
5
Laboratory for Immune Regulation, World Premier International Research Center Initiative Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0861, Japan; Laboratory for Host Defense, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan.
6
PRESTO, Japan Science and Technology Agency, Chiyoda-ku, Tokyo 102-0076, Japan; Department of Physiology, Graduate School of Medicine, Yokohama City University, Yokohama, Kanagawa 236-0004, Japan.
7
Department of Molecular Bacteriology and Immunology, Graduate School of Medicine, University of the Ryukyus, Nakagami-gun, Okinawa 903-0125, Japan.
8
Laboratory for Histogenetic Dynamics, RIKEN Center for Developmental Biology, Chuo-ku, Kobe 650-0047, Japan.
9
Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan; Department of Human Genome Research, Kazusa DNA Research Institute, Kisarazu, Chiba 292-0818, Japan.
10
Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan; CREST, Japan Science and Technology Agency, Chiyoda-ku, Tokyo 102-0076, Japan. Electronic address: miura@mol.f.u-tokyo.ac.jp.

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.

PMID:
25127135
DOI:
10.1016/j.celrep.2014.07.012
[Indexed for MEDLINE]
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