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Sensing of cytosolic LPS through caspy2 pyrin domain mediates noncanonical inflammasome activation in zebrafish

Author

Listed:
  • Dahai Yang

    (East China University of Science and Technology)

  • Xin Zheng

    (East China University of Science and Technology)

  • Shouwen Chen

    (East China University of Science and Technology)

  • Zhuang Wang

    (East China University of Science and Technology)

  • Wenting Xu

    (East China University of Science and Technology)

  • Jinchao Tan

    (East China University of Science and Technology)

  • Tianjian Hu

    (East China University of Science and Technology)

  • Mingyu Hou

    (East China University of Science and Technology)

  • Wenhui Wang

    (East China University of Science and Technology)

  • Zhaoyan Gu

    (East China University of Science and Technology)

  • Qiyao Wang

    (East China University of Science and Technology
    Qingdao National Laboratory for Marine Science and Technology
    Shanghai Engineering Research Center of Marine Cultured Animal Vaccines
    Shanghai Collaborative Innovation Center for Biomanufacturing)

  • Ruilin Zhang

    (Shanghai Collaborative Innovation Center for Biomanufacturing
    Fudan University)

  • Yuanxing Zhang

    (East China University of Science and Technology
    Qingdao National Laboratory for Marine Science and Technology
    Shanghai Engineering Research Center of Marine Cultured Animal Vaccines
    Shanghai Collaborative Innovation Center for Biomanufacturing)

  • Qin Liu

    (East China University of Science and Technology
    Qingdao National Laboratory for Marine Science and Technology
    Shanghai Engineering Research Center of Marine Cultured Animal Vaccines
    Shanghai Collaborative Innovation Center for Biomanufacturing)

Abstract

The noncanonical inflammasome is critical for cytosolic sensing of Gram-negative pathogens. Here, we show that bacterial infection induces caspy2 activation in zebrafish fibroblasts, which mediates pyroptosis via a caspase-5-like activity. Zebrafish caspy2 binds directly to lipopolysaccharide via the N-terminal pyrin death domain, resulting in caspy2 oligomerization, which is critical for pyroptosis. Furthermore, we show that caspy2 is highly expressed in the zebrafish gut and is activated during infection. Knockdown of caspy2 expression impairs the ability of zebrafish to restrict bacterial invasion in vivo, and protects larvae from lethal sepsis. Collectively, our results identify a crucial event in the evolution of pattern recognition into the death domain superfamily-mediated intracellular lipopolysaccharide-sensing pathway in innate immunity.

Suggested Citation

  • Dahai Yang & Xin Zheng & Shouwen Chen & Zhuang Wang & Wenting Xu & Jinchao Tan & Tianjian Hu & Mingyu Hou & Wenhui Wang & Zhaoyan Gu & Qiyao Wang & Ruilin Zhang & Yuanxing Zhang & Qin Liu, 2018. "Sensing of cytosolic LPS through caspy2 pyrin domain mediates noncanonical inflammasome activation in zebrafish," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04984-1
    DOI: 10.1038/s41467-018-04984-1
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