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

  • Nat Commun. 2018 Aug 3;9(1):3052. doi: 10.1038/s41467-018-04984-1.
Dahai Yang  1 ,  Xin Zheng  1 ,  Shouwen Chen  1 ,  Zhuang Wang  1 ,  Wenting Xu  1 ,  Jinchao Tan  1 ,  Tianjian Hu  1 ,  Mingyu Hou  1 ,  Wenhui Wang  1 ,  Zhaoyan Gu  1 ,  Qiyao Wang  1  2  3  4 ,  Ruilin Zhang  4  5 ,  Yuanxing Zhang  1  2  3  4 ,  Qin Liu  6  7  8  9
Affiliations
  • 1. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China.
  • 2. Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266071, China.
  • 3. Shanghai Engineering Research Center of Marine Cultured Animal Vaccines, Shanghai, 200237, China.
  • 4. Shanghai Collaborative Innovation Center for Biomanufacturing, Shanghai, 200237, China.
  • 5. State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200433, China.
  • 6. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China. [email protected].
  • 7. Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266071, China. [email protected].
  • 8. Shanghai Engineering Research Center of Marine Cultured Animal Vaccines, Shanghai, 200237, China. [email protected].
  • 9. Shanghai Collaborative Innovation Center for Biomanufacturing, Shanghai, 200237, China. [email protected].
PMID: 30076291 DOI: 10.1038/s41467-018-04984-1
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.

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