PDF(Pubmed)
Abstract：
Studies of the interplay between metabolism and immunity, known as immunometabolism, is steadily transforming immunological research into new understandings of how environmental cues like diet are affecting innate and adaptive immune responses. The aim of this study was to explore antiviral transcriptomic responses under various levels of polyunsaturated fatty acid. Atlantic salmon kidney cells (ASK cell line) were incubated for one week in different levels of the unsaturated n-3 eicosapentaneoic acid (EPA) resulting in cellular levels ranging from 2-20% of total fatty acid. These cells were then stimulated with the viral mimic and interferon inducer poly I:C (30 ug/ml) for 24 hours before total RNA was isolated and sequenced for transcriptomic analyses. Up to 200 uM EPA had no detrimental effects on cell viability and induced very few transcriptional changes in these cells. However, in combination with poly I:C, our results shows that the level of EPA in the cellular membranes exert profound dose dependent effects of the transcriptional profiles induced by this treatment. Metabolic pathways like autophagy, apelin and VEGF signaling were attenuated by EPA whereas transcripts related to fatty acid metabolism, ferroptosis and the PPAR signaling pathways were upregulated. These results suggests that innate antiviral responses are heavily influenced by the fatty acid profile of salmonid cells and constitute another example of the strong linkage between general metabolic pathways and inflammatory responses.
摘要：
代谢和免疫之间的相互作用的研究，被称为免疫代谢，正在稳步地将免疫学研究转化为对饮食等环境线索如何影响先天和适应性免疫反应的新理解。这项研究的目的是探索不同水平的多不饱和脂肪酸下的抗病毒转录组反应。将大西洋鲑鱼肾细胞（ASK细胞系）在不同水平的不饱和n-3二十碳五烷酸（EPA）中孵育一周，导致细胞水平占总脂肪酸的2-20％。然后用病毒模拟物和干扰素诱导物polyI:C(30ug/ml)刺激这些细胞24小时,然后分离总RNA并测序用于转录组学分析。高达200uM的EPA对细胞活力没有有害影响,并且在这些细胞中诱导非常少的转录变化。然而,结合聚I：C，我们的结果表明，细胞膜中EPA的水平对该治疗诱导的转录谱产生了深远的剂量依赖性影响。像自噬这样的代谢途径，apelin和VEGF信号被EPA减弱，而与脂肪酸代谢相关的转录本，铁凋亡和PPAR信号通路上调。这些结果表明，先天的抗病毒反应受到鲑鱼细胞脂肪酸谱的严重影响，并构成了一般代谢途径和炎症反应之间强联系的另一个例子。
