Pathogen blockade of TAK1 triggers caspase-8–dependent cleavage of gasdermin D and cell death
-
- Pontus Orning
- Program in Innate Immunity, Department of Medicine, Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
-
- Dan Weng
- Program in Innate Immunity, Department of Medicine, Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
-
- Kristian Starheim
- Program in Innate Immunity, Department of Medicine, Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
-
- Dmitry Ratner
- Program in Innate Immunity, Department of Medicine, Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
-
- Zachary Best
- Program in Innate Immunity, Department of Medicine, Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
-
- Bettina Lee
- Department of Physiological Chemistry, Genentech, South San Francisco, CA 94080, USA.
-
- Alexandria Brooks
- Program in Innate Immunity, Department of Medicine, Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
-
- Shiyu Xia
- Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, and Program in Cellular and Molecular Medicine, Boston Children’s Hospital, Boston, MA 02115, USA.
-
- Hao Wu
- Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, and Program in Cellular and Molecular Medicine, Boston Children’s Hospital, Boston, MA 02115, USA.
-
- Michelle A. Kelliher
- Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
-
- Scott B. Berger
- Pattern Recognition Receptor Discovery Performance Unit, Immuno-inflammation Therapeutic Area, GlaxoSmithKline, Collegeville, PA 19426, USA.
-
- Peter J. Gough
- Pattern Recognition Receptor Discovery Performance Unit, Immuno-inflammation Therapeutic Area, GlaxoSmithKline, Collegeville, PA 19426, USA.
-
- John Bertin
- Pattern Recognition Receptor Discovery Performance Unit, Immuno-inflammation Therapeutic Area, GlaxoSmithKline, Collegeville, PA 19426, USA.
-
- Megan M. Proulx
- Department of Microbiology and Physiology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
-
- Jon D. Goguen
- Department of Microbiology and Physiology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
-
- Nobuhiko Kayagaki
- Department of Physiological Chemistry, Genentech, South San Francisco, CA 94080, USA.
-
- Katherine A. Fitzgerald
- Program in Innate Immunity, Department of Medicine, Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
-
- Egil Lien
- Program in Innate Immunity, Department of Medicine, Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
書誌事項
- 公開日
- 2018-11-30
- DOI
-
- 10.1126/science.aau2818
- 公開者
- American Association for the Advancement of Science (AAAS)
この論文をさがす
説明
<jats:title>Caspase-8 is a player in pyroptosis</jats:title> <jats:p> The activation of certain pattern-recognition receptors by pathogen-associated molecular patterns results in the formation of inflammasome complexes. Inflammasome complexes can initiate both the maturation of inflammatory cytokines and pyroptotic cell death via the caspase-mediated cleavage of gasdermin D (GSDMD). As of now, the only known regulators of GSDMD in macrophages are caspase-1 and caspase-11. Orning <jats:italic>et al.</jats:italic> report an additional pathway controlling GSDMD processing. YopJ, an effector molecule produced by <jats:italic>Yersinia</jats:italic> (the causative agent of plague), inhibits TAK1–IκB kinase signaling. This, in turn, results in caspase-8–directed cleavage of GSDMD, pyroptosis, and the release of interleukin 1β (IL-1β) and IL-18. Thus, in the arms race between host and pathogen, the host recognizes signaling disturbances as pathogenic and counters with inflammation and cell death. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6418" page="1064" related-article-type="in-this-issue" vol="362" xlink:href="10.1126/science.aau2818">1064</jats:related-article> </jats:p>
収録刊行物
-
- Science
-
Science 362 (6418), 1064-1069, 2018-11-30
American Association for the Advancement of Science (AAAS)