Xu Xuan, Liu Yiying, Li Xingchun, Zhang Pei, Lin Fengjun, Chen Chonghui, Zhang Xiaoxu, Li Chao, Fu Qiang
School of Marine Science and Engineering, Qingdao Agricultural University, Qingdao, 266109, China.
School of Marine Science and Engineering, Qingdao Agricultural University, Qingdao, 266109, China.
Dev Comp Immunol. 2025 May;167:105387. doi: 10.1016/j.dci.2025.105387. Epub 2025 May 8.
Cathepsin D (CTSD), a ubiquitous aspartate hydrolase in eukaryotes, is predominantly localized in lysosomes and involved in the process of substance hydrolysis. While extensive studies have highlighted the importance of CTSD in various physiological and pathological conditions in mammals, its functional roles and mechanisms in fish in responses to bacterial infections remain poorly understood. In this study, two CTSD genes, SsCTSDa and SsCTSDb, were identified in Sebastes schlegelii, and their characteristics were systematically investigated through phylogenetic analysis, syntenic analysis, and tissue-specific expression profiling under both healthy and bacterial infection conditions. Additionally, their immune-related properties, including subcellular localization, microbial ligand-binding capacity, and agglutination activity, were explored. Firstly, SsCTSDa encodes a 396-amino acid protein with a molecular mass of 43.01 kDa, while SsCTSDb encodes a 339-amino acid protein with a molecular mass of 43.36 kDa. Furthermore, both genes were ubiquitously expressed in all examined tissues, with the highest expression levels observed in the spleen. Moreover, SsCTSDa and SsCTSDb exhibited distinct expression patterns following bacterial infection, showing significant upregulation in the kidney and gill. Functional assays demonstrated that recombinant SsCTSDa (rSsCTSDa) and SsCTSDb (rSsCTSDb) exhibited strong binding affinity to microbial ligands, including LPS, PGN, LTA, and Poly (I:C). Notably, rSsCTSDb displayed broad-spectrum agglutination activity against both Gram-positive and Gram-negative bacteria, whereas rSsCTSDa specifically agglutinated Gram-negative bacteria. This study suggests that CTSD plays a crucial role in the immune responses of teleosts, highlighting its potential as a key mediator in host-pathogen interactions.
组织蛋白酶D(CTSD)是真核生物中一种普遍存在的天冬氨酸水解酶,主要定位于溶酶体并参与物质水解过程。虽然大量研究强调了CTSD在哺乳动物各种生理和病理条件下的重要性,但其在鱼类应对细菌感染中的功能作用和机制仍知之甚少。在本研究中,在许氏平鲉中鉴定出两个CTSD基因,即SsCTSDa和SsCTSDb,并通过系统发育分析、共线性分析以及在健康和细菌感染条件下的组织特异性表达谱分析对其特征进行了系统研究。此外,还探索了它们的免疫相关特性,包括亚细胞定位、微生物配体结合能力和凝集活性。首先,SsCTSDa编码一种分子量为43.01 kDa的396个氨基酸的蛋白质,而SsCTSDb编码一种分子量为43.36 kDa的339个氨基酸的蛋白质。此外,这两个基因在所有检测组织中均有广泛表达,在脾脏中表达水平最高。而且,SsCTSDa和SsCTSDb在细菌感染后表现出不同的表达模式,在肾脏和鳃中显著上调。功能分析表明,重组SsCTSDa(rSsCTSDa)和SsCTSDb(rSsCTSDb)对包括脂多糖(LPS)、肽聚糖(PGN)、脂磷壁酸(LTA)和聚肌苷酸胞苷酸(Poly (I:C))在内的微生物配体表现出强烈的结合亲和力。值得注意的是,rSsCTSDb对革兰氏阳性菌和革兰氏阴性菌均表现出广谱凝集活性,而rSsCTSDa则特异性凝集革兰氏阴性菌。本研究表明,CTSD在硬骨鱼的免疫反应中起关键作用,突出了其作为宿主 - 病原体相互作用中关键介质的潜力。