Lin Tianxiang, Liu Lu, Zeng Liang, Zhao Congxin, Xiao Shu, Ma Haitao, Li Jun, Mao Fan, Qin Yanping, Zhang Yuehuan, Zhang Yang, Xiang Zhiming, Yu Ziniu
Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
Int J Biol Macromol. 2025 Mar;296:139632. doi: 10.1016/j.ijbiomac.2025.139632. Epub 2025 Jan 9.
NLR inflammasomes recognize pathogen-associated molecular patterns (PAMPs), triggering Caspase-1 activation and leading to gasdermin D (GSDMD)-mediated pyroptosis, a crucial immune response in mammals. The functional GSDME-mediated pyroptosis has been reported in invertebrates, yet the existence of an NLR-Caspase-GSDME axis mediating pyroptosis signaling cascades remains unclear. In this study, we reported an NLRC4 homolog named ChNLRC4, a pattern recognition receptor from the oyster Crassostrea hongkongensis that is able to bind to LPS and Lys-type PGN through its LRR domain. ChNLRC4 interacted with ChCaspase-1 through CARD-CARD domain homotypic interactions and enhanced ChCaspase-1 activity. Additionally, overexpression of ChNLRC4 promoted ChCaspase-1-mediated cleavage of ChGSDME, leading to pyroptosis in HEK293T cells. Furthermore, knockdown of chnlrc4 resulted in a significant reduction in the death rate of hemocytes, immune infiltration of hemocytes, cilium shedding, and bacterial clearance. Collectively, this study provides insight into the role of NLR within the pyroptosis signaling pathway in oysters.
NLR炎性小体识别病原体相关分子模式（PAMPs），触发半胱天冬酶-1激活并导致gasdermin D（GSDMD）介导的细胞焦亡，这是哺乳动物中的一种关键免疫反应。功能性GSDME介导的细胞焦亡已在无脊椎动物中报道，但介导细胞焦亡信号级联反应的NLR-半胱天冬酶-GSDME轴的存在仍不清楚。在本研究中，我们报道了一种名为ChNLRC4的NLRC4同源物，它是香港牡蛎的一种模式识别受体，能够通过其LRR结构域与LPS和赖氨酸型PGN结合。ChNLRC4通过CARD-CARD结构域同型相互作用与ChCaspase-1相互作用并增强ChCaspase-1活性。此外，ChNLRC4的过表达促进了ChCaspase-1介导的ChGSDME裂解，导致HEK293T细胞发生细胞焦亡。此外，敲低chnlrc4导致血细胞死亡率、血细胞免疫浸润、纤毛脱落和细菌清除率显著降低。总的来说，本研究深入了解了NLR在牡蛎细胞焦亡信号通路中的作用。
