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大西洋鳕鱼疫苗反应的全转录组分析揭示了适应性免疫的微妙变化。

Whole transcriptome analysis of the Atlantic cod vaccine response reveals subtle changes in adaptive immunity.

机构信息

Centre for Ecological and Evolutionary Synthesis (CEES), Department of Biosciences, University of Oslo, Oslo, Norway.

Centre for Ecological and Evolutionary Synthesis (CEES), Department of Biosciences, University of Oslo, Oslo, Norway.

出版信息

Comp Biochem Physiol Part D Genomics Proteomics. 2019 Sep;31:100597. doi: 10.1016/j.cbd.2019.100597. Epub 2019 May 28.

Abstract

Atlantic cod has lost the Major Histocompatibility complex class II pathway - central to pathogen presentation, humoral response and immunity. Here, we investigate the immunological response of Atlantic cod subsequent to dip vaccination with Vibrioanguillarum bacterin using transcriptome sequencing. The experiment was conducted on siblings from an Atlantic cod family found to be highly susceptible towards vibriosis where vaccination has demonstrated improved pathogen resistance. Gene expression analyses at 2, 4, 21 and 42 days post vaccination revealed GO-term enrichment for muscle, neuron and metabolism-related pathways. In-depth characterization of immune-related GO terms demonstrated down-regulation of MHCI antigen presentation, C-type lectin receptor signaling and granulocyte activation over time. Phagocytosis, interferon-gamma signaling and negative regulation of innate immunity were increasingly up-regulated over time. Individual differentially expressed immune genes implies weak initiation of acute phase proteins with little or no inflammation. Furthermore, gene expression indicates presence of T-cells, NK-like cells, B-cells and monocytes/macrophages. Three MHCI transcripts were up-regulated with B2M and SEC61. Overall, we find no clear immune-related transcriptomic response which could be attributed to Atlantic cod's alternative immune system. However, we cannot rule out that this response is related to vaccination protocol/sampling strategy. Earlier functional studies demonstrate significant memory in Atlantic cod post dip vaccination and combined with our results indicate the presence of other adaptive immunity mechanisms. In particular, we suggest that further investigations should look into CD8+ memory T-cells, γδ T-cells, T-cell independent memory or memory induced through NK-like/other lymphoid cells locally in the mucosal lining for this particular vaccination strategy.

摘要

北大西洋鳕鱼失去了主要组织相容性复合体 II 途径——这是病原体呈递、体液反应和免疫的核心。在这里,我们使用转录组测序研究了大西洋鳕鱼在接种 Vibrioanguillarum 菌苗后的免疫反应。该实验是在一个对弧菌病高度易感的大西洋鳕鱼家族的兄弟姐妹身上进行的,接种疫苗已证明可提高病原体的抵抗力。接种后 2、4、21 和 42 天的基因表达分析显示肌肉、神经元和代谢相关途径的 GO 术语富集。对免疫相关 GO 术语的深入分析表明,MHCI 抗原呈递、C 型凝集素受体信号和粒细胞激活随时间呈下调趋势。吞噬作用、干扰素-γ信号和先天免疫的负调控随时间逐渐上调。免疫相关差异表达基因表明急性相蛋白的起始较弱,炎症很少或没有。此外,基因表达表明存在 T 细胞、NK 样细胞、B 细胞和单核细胞/巨噬细胞。三种 MHCI 转录物与 B2M 和 SEC61 一起上调。总的来说,我们没有发现明显的与免疫相关的转录组反应,这可能归因于大西洋鳕鱼的替代免疫系统。然而,我们不能排除这种反应与疫苗接种方案/采样策略有关。早期的功能研究表明,大西洋鳕鱼在接种菌苗后具有显著的记忆能力,结合我们的研究结果表明,存在其他适应性免疫机制。特别是,我们建议进一步的研究应该关注 CD8+记忆 T 细胞、γδ T 细胞、T 细胞非依赖性记忆或通过 NK 样/其他淋巴样细胞在粘膜衬里诱导的记忆,用于这种特定的疫苗接种策略。

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