State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
College of Advanced Agricultural Sciences, University of Chinese Academy of Sciences, Beijing, China.
Front Immunol. 2022 Jul 11;13:939464. doi: 10.3389/fimmu.2022.939464. eCollection 2022.
In teleost fish, the nucleotide polymorphisms of histone H2A significantly affect the resistance or susceptibility of zebrafish to infection. Whether histone H2A variants can enhance the resistance of grass carp to infection remains unclear. Here, the effects of 7 previously obtained variants (gcH2A-1gcH2A-7) and 5 novel histone H2A variants (gcH2A-11, gcH2A-13gcH2A-16) in response to infection were investigated. It was found that these histone H2A variants could be divided into type I and II. Among them, 5 histone H2A variants had no any effects on the infection, however 7 histone H2A variants had antibacterial activity against infection. The gcH2A-4 and gcH2A-11, whose antibacterial activity was the strongest in type I and II histone H2A variants respectively, were picked out for yeast expression. Transcriptome data for the samples from the intestines of grass carp immunized with the engineered expressing PYD1, gcH2A-4 or gcH2A-11 revealed that 5 and 12 immune-related signaling pathways were significantly enriched by gcH2A-4 or gcH2A-11, respectively. For the engineered expressing gcH2A-4, NOD-like receptor and Toll-like receptor signaling pathways were enriched for up-regulated DEGs. Besides NOD-like receptor and Toll-like receptor signaling pathways, the engineered expressing gcH2A-11 also activated Cytosolic DNA-sensing pathway, RIG-I-like receptor signaling pathway and C-type lectin receptor signaling pathway. Furthermore, grass carp were immunized with the engineered expressing PYD1, gcH2A-4 or gcH2A-11 for 1 month and challenged with These grass carp immunized with gcH2A-4 or gcH2A-11 showed lower mortality and fewer numbers of than did the control group. All these results suggest that gcH2A-4 and gcH2A-11 play important roles in evoking the innate immune responses and enhancing disease resistance of grass carp against infection.
在硬骨鱼类中,组蛋白 H2A 的核苷酸多态性显著影响斑马鱼对 的易感性和抗性。组蛋白 H2A 变体是否可以增强草鱼对 的抗性尚不清楚。本研究中,研究了之前获得的 7 种变体(gcH2A-1gcH2A-7)和 5 种新型组蛋白 H2A 变体(gcH2A-11、gcH2A-13gcH2A-16)在应对 感染时的作用。结果发现,这些组蛋白 H2A 变体可分为 I 型和 II 型。其中,5 种组蛋白 H2A 变体对 感染没有任何影响,而 7 种组蛋白 H2A 变体对 感染具有抗菌活性。在 I 型和 II 型组蛋白 H2A 变体中,抗菌活性最强的 gcH2A-4 和 gcH2A-11 被挑出来进行酵母表达。用工程菌表达 PYD1、gcH2A-4 或 gcH2A-11 免疫草鱼后肠样本的转录组数据表明,gcH2A-4 或 gcH2A-11 分别显著富集了 5 和 12 条免疫相关信号通路。对于表达 gcH2A-4 的工程菌,NOD 样受体和 Toll 样受体信号通路中上调的 DEGs 被富集。除了 NOD 样受体和 Toll 样受体信号通路外,表达 gcH2A-11 的工程菌还激活了细胞质 DNA 感应通路、RIG-I 样受体信号通路和 C 型凝集素受体信号通路。此外,草鱼用表达 PYD1、gcH2A-4 或 gcH2A-11 的工程菌免疫 1 个月后,用 攻毒。与对照组相比,gcH2A-4 或 gcH2A-11 免疫的草鱼死亡率更低, 数量更少。所有这些结果表明,gcH2A-4 和 gcH2A-11 在引发草鱼固有免疫反应和增强草鱼对 感染的抗性方面发挥重要作用。