文献类型：期刊文献

英文题名：leSensing of cytosolic LPS through caspy2 pyrin domain mediates noncanonical inflammasome activation in zbrafish

作者：Yang, Dahai[1];Zheng, Xin[1];Chen, Shouwen[1];Wang, Zhuang[1];Xu, Wenting[1];Tan, Jinchao[1];Hu, Tianjian[1];Hou, Mingyu[1];Wang, Wenhui[1];Gu, Zhaoyan[1];Wang, Qiyao[1,2,3,4];Zhang, Ruilin[4,5];Zhang, Yuanxing[1,2,3,4];Liu, Qin[1,2,3,4]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Qingdao Natl Lab Marine Sci & Technol, Lab Marine Biol & Biotechnol, Qingdao 266071, Peoples R China;[3]Shanghai Engn Res Ctr Marine Cultured Anim Vaccin, Shanghai 200237, Peoples R China;[4]Shanghai Collaborat Innovat Ctr Biomfg, Shanghai 200237, Peoples R China;[5]Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200433, Peoples R China

年份：2018

卷号：9

外文期刊名：NATURE COMMUNICATIONS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000440652500004)】；

基金：We thank Dr. Feng Shao from NIBs for sharing CASP4-/- and GSDMD-/- HeLa cells, and providing useful advice. This work was supported by the National Natural Science Foundation of China (Nos. 31472308 (Q.L.) and 31430090 (Y.Z.)) and the Fundamental Research Funds for the Central Universities (No. 222201714022 (D.Y.)). Dahai Yang was supported by the Young Elite Scientists Sponsorship Program by CAST No. 2016QNRC001, Shanghai Pujiang Program No. 16PJD020, Shanghai Chenguang Program No. 16CG33, and Talent Program of School of Biotechnology in East China University of Science and Technology. Ruilin Zhang was supported by the National Natural Science Foundation of China (No. 31571492).

语种：英文

摘要：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.