State Key Laboratory of Estuarine and Coastal Research, School of Life Sciences, East China Normal University, Shanghai 200241, China.
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, Hubei, China.
Dev Comp Immunol. 2021 Feb;115:103884. doi: 10.1016/j.dci.2020.103884. Epub 2020 Oct 9.
Tumor necrosis factors (TNFs) are pleiotropic cytokines with important functions in homeostasis and disease pathogenesis. Recent advances have shown that TNFs are also involved in the regulation of adaptive immune responses. However, the knowledge about how TNF participates in and regulates adaptive immune response in early vertebrates is still limited. In present study, we identified two isoforms of TNF, TNF-α and TNF-β, from Nile tilapia Oreochromis niloticus (On-TNF-α and β). After analyzing the sequence characteristics, we investigated their regulatory roles in adaptive immune response of this fish species. On-TNF-α and β are evolutionarily conserved compare with their homologs from other vertebrates. Both TNFs were distributed in a wide range of tissues in O. niloticus, and with relative higher expression level in gill. After the animals were infected by Streptococcus agalactiae, mRNA levels of On-TNF-α and TNF-β in spleen lymphocytes were significantly upregulated during the primary response stage of adaptive immunity. Meanwhile, both TNF proteins in spleen lymphocytes were also dramatically elevated during the adaptive immune stage after bacterial infection. These results indicate the potential participation of On-TNF-α and TNF-β in adaptive immune response of Nile tilapia. Furthermore, On-TNF-α and β transcripts were obviously augmented, once spleen lymphocytes were activated by T cell-specific mitogen PHA. More importantly, both recombinant On-TNF-α and β could induce the apoptosis of head-kidney leukocytes of Nile tilapia. And On-TNF-β but not On-TNF-α promoted the apoptosis by activating caspase-8 in the target cells. Altogether, our study revealed that TNF-α and TNF-β participated in the lymphocyte-mediated adaptive immune response of Nile tilapia by initiating the apoptosis, and thus shed novel perspective for the regulatory mechanism of adaptive immunity in teleost.
肿瘤坏死因子 (TNFs) 是一类具有重要生理功能的多效细胞因子，在疾病的发病机制中也发挥着重要作用。最近的研究进展表明，TNFs 还参与了适应性免疫反应的调节。然而，关于 TNF 如何参与和调节早期脊椎动物的适应性免疫反应的知识仍然有限。在本研究中，我们从尼罗罗非鱼 (Oreochromis niloticus) 中鉴定出两种 TNF 同工型，TNF-α 和 TNF-β (On-TNF-α 和 β)。在分析了它们的序列特征后，我们研究了它们在这种鱼类适应性免疫反应中的调节作用。On-TNF-α 和 β 与其他脊椎动物的同源物相比具有进化保守性。TNFs 在尼罗罗非鱼的广泛组织中均有分布，在鳃中的表达水平相对较高。在动物被无乳链球菌感染后，脾脏淋巴细胞中 On-TNF-α 和 TNF-β 的 mRNA 水平在适应性免疫的初级反应阶段显著上调。同时，在细菌感染后的适应性免疫阶段，脾脏淋巴细胞中的两种 TNF 蛋白也显著升高。这些结果表明 On-TNF-α 和 TNF-β 可能参与了尼罗罗非鱼的适应性免疫反应。此外，一旦脾脏淋巴细胞被 T 细胞特异性有丝分裂原 PHA 激活，On-TNF-α 和 β 的转录本就会明显增加。更重要的是，重组 On-TNF-α 和 β 均可诱导尼罗罗非鱼头肾白细胞凋亡。而且 On-TNF-β 而不是 On-TNF-α 通过激活靶细胞中的 caspase-8 来促进细胞凋亡。总之，我们的研究揭示了 TNF-α 和 TNF-β 通过启动细胞凋亡参与了尼罗罗非鱼淋巴细胞介导的适应性免疫反应，为硬骨鱼类适应性免疫的调节机制提供了新的视角。
