State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, 410081, China.
Department of Nutrition, Xiangya Hospital, Central South University, Changsha, 410008, China.
Dev Comp Immunol. 2021 Mar;116:103924. doi: 10.1016/j.dci.2020.103924. Epub 2020 Nov 10.
Cytidine/uridine monophosphate kinase 2 (CMPK2) is a thymidylate kinase and in mammals is known to be involved in mitochondrial DNA (mtDNA) synthesis and antiviral immunity. However, very little is known about the function of CMPK2 in fish. With an aim to elucidate the antimicrobial mechanism of CMPK2 in fish, we in this study examined the function of CMPK2 from triploid crucian carp (3nCmpk2). 3nCmpk2 is 426 residues in length and possesses the conserved thymidylate kinase domain. The deduced amino acid sequence of 3nCmpk2 shares 53.2%-99.1% overall identities with the CMPK2 of several fish species. Quantitative real time RT-PCR (qRT-PCR) analysis showed that 3nCmpk2 expression occurred in multiple tissues and was upregulated by bacterial infection in a time-dependent manner. Recombinant 3nCmpk2 (r3nCmpk2) induced mtDNA synthesis and NLRP3 activation. Overexpression of 3nCmpk2 protects the intestinal barrier and hampers the bacterial colonization in fish tissues. These results provide the first evidence that 3nCmpk2 is involved in host innate immunity and plays a protective role in antimicrobial responses during bacterial infection.
胞苷/尿苷一磷酸激酶 2（CMPK2）是胸苷激酶，在哺乳动物中被认为参与线粒体 DNA（mtDNA）合成和抗病毒免疫。然而，关于鱼类中 CMPK2 的功能知之甚少。为了阐明鱼类 CMPK2 的抗菌机制，本研究检测了三倍体鲫鱼（3nCmpk2）的 CMPK2 功能。3nCmpk2 长 426 个残基，具有保守的胸苷激酶结构域。3nCmpk2 的推导氨基酸序列与几种鱼类的 CMPK2 具有 53.2%-99.1%的整体同一性。定量实时 RT-PCR（qRT-PCR）分析显示，3nCmpk2 在多种组织中表达，并随细菌感染呈时间依赖性上调。重组 3nCmpk2（r3nCmpk2）诱导 mtDNA 合成和 NLRP3 激活。3nCmpk2 的过表达可保护肠道屏障并阻碍细菌在鱼组织中的定植。这些结果首次表明 3nCmpk2 参与宿主固有免疫，并在细菌感染期间的抗菌反应中发挥保护作用。
