文献类型：期刊文献

英文题名：Dual function of a turbot inflammatory caspase in mediating both canonical and non-canonical inflammasome activation

作者：Chen, Shouwen[1];Jin, Peng[1];Chen, Hao[1];Wu, Di[1];Li, Shuxin[1];Zhang, Yuanxing[1,2,3];Liu, Qin[1,3];Yang, Dahai[1,3]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Southern Marine Sci & Engn Guangdong Lab Zhuhai, Zhuhai 519000, Peoples R China;[3]Shanghai Engn Res Ctr Marine Cultured Anim Vaccin, Shanghai 200237, Peoples R China

年份：2021

卷号：121

外文期刊名：DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000651145200003)】；

基金：We thank Prof. Kangsen Mai from Ocean University of China for sharing turbot TMF cells. This work was supported by the NSFC (No. 32002429) to S.C., the Science and Technology Innovation Program by the STCSM (No.20ZR1415500) to D.Y., the China Postdoctoral Science Foundation (No. 2020M671033) to S.C.

语种：英文

外文关键词：Turbot; Inflammatory caspase; Cytosolic LPS receptor; NLRP3 inflammasome; GSDME; Pyroptosis; Antibacterial activity

摘要：Host protective inflammatory caspase activity must be tightly regulated to prevent pathogens infection, however, the inflammatory caspase-engaged inflammasome activation in teleost fish remains largely unknown. In this study, we reveal a bifurcated evolutionary role of the inflammatory caspase in mediating both non-canonical and canonical inflammasome pathways in teleost fish. Through characterization of a unique inflammatory SmCaspase from the teleost Scophthalmus maximus (turbot), we found it can directly recognize cytosolic lipopolysaccharide (LPS) via its N-terminal CARD domain, resulting in caspase-5-like proteolytic enzyme activity-mediated pyroptosis in Turbot Muscle Fibroblasts. Interestingly, we also found that this inflammatory caspase can be recruited to SmNLRP3-SmASC to form the NLRP3 inflammasome complex, engaging the SmIL-1 beta release in Head Kidneyderived Macrophages. Consequently, the SmCaspase activation can recognize and cleave the SmGSDMEb to release its N-terminal domain, mediating both pyroptosis and bactericidal activities. Furthermore, the SmCaspase-SmGSDMEb axis-gated pyroptosis governs the bacterial clearance and epithelial desquamation in fish gill filaments in vivo. To our knowledge, this study is the first to identify an inflammatory caspase acting as a central coordinator in NLRP3 inflammasome, as well as a cytosolic LPS receptor; thus uncovering a previously unrecognized function of inflammatory caspase in turbot innate immunity.