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NLRX1 in fish: A negative regulator of innate immunity during Edwardsiella piscicida infection via targeting TRAF6 through the NACHT domain  ( SCI-EXPANDED收录)  

文献类型:期刊文献

英文题名:NLRX1 in fish: A negative regulator of innate immunity during Edwardsiella piscicida infection via targeting TRAF6 through the NACHT domain

作者:Wang, Binliang[1];Lan, Xuan[1];Lin, Sihan[1];Xu, Hong[1];Zhang, Xiaodong[1];Yin, Junxia[1];Hu, Yiwei[1]

机构:[1]Shaoxing Univ, Sch Life & Environm Sci, Huancheng West Rd 508, Shaoxing 312000, Peoples R China

年份:2025

卷号:594

外文期刊名:AQUACULTURE

收录:SCI-EXPANDED(收录号:WOS:001294785100001)、、WOS

基金:This research was supported by Zhejiang Provincial Natural Science Foundation of China under Grant No. LQ20C190007.

语种:英文

外文关键词:NLRX1; Immune regulation; Pro-inflammatory cytokines; Antibacterial immunity

外文摘要:NLRX1, an important member of regulatory Nod-like receptors (NLRs), exerts multifaceted roles in the regulation of mammalian innate immunity. However, the function and mechanism of fish NLRX1 in antibacterial immune regulation remain unclear. In this study, the zebrafish NLRX1 was cloned and characterized. Phylogenetic analysis demonstrated that zebrafish NLRX1 clustered closely with other NLRX1 homologs in fish and exhibited 84.6%-87.4% sequence identities to that of cyprinid fish. Subcellular localization analysis showed that zebrafish NLRX1 located both in the mitochondrial and cytoplasmic compartments of transfected cells. Functionally, zebrafish NLRX1 expression was dramatically induced upon Edwardsiella piscicida infection. Overexpression of NLRX1 promoted E. piscicida proliferation and impaired survival rate both in vitro and in vivo. Furthermore, the up-regulation of pro-inflammatory cytokines (IL8, IL6, TNF alpha, IL1 beta) and antibacterial gene defbl2 was reduced in E. piscicida infected larvae that were microinjected with NLRX1. Consistent with these observations, the antibacterial ability was significantly enhanced in NLRX1 knockdown cells. Mechanistically, zebrafish NLRX1 interacted with tumor necrosis factor receptor-associated factor 6 (TRAF6) through its NACHT domain, attenuating TRAF6-mediated antibacterial innate immunity. Our study sheds light on the negative regulatory role of fish NLRX1 in antibacterial immunity, offering potential applications in fish disease management and immune regulation.

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