Interferon-α2b against microbes through promoting biosynthesis of unsaturated fatty acids.
Interferon-α2b against microbes through promoting biosynthesis of unsaturated fatty acids.
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DOI：
10.1021/pr500592x
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发表时间：
2014-08
影响因子：
4.4
通讯作者：
Xian-liang Zhao;Chang-wen Wu;Xuan-xian Peng;Hui Li
中科院分区：
文献类型：
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作者：
Xian-liang Zhao;Chang-wen Wu;Xuan-xian Peng;Hui Li
干扰素（IFN）家族是一大类参与天然免疫应答的细胞因子。然而，IFN是否通过代谢途径发挥抗微生物特性在很大程度上是未知的。本研究以斑马鱼（Danio rerio）为实验动物，研究了干扰素-α2b（IFN-L、IFN-M和IFN-H）对斑马鱼体液代谢物的影响。在鉴定的67种化合物中，与对照组相比，三组中分别鉴定出19、28和29种代谢物的丰度差异。共获得41个差异代谢产物组成IFN-α 2b依赖性代谢物组，其中13个在3个IFN-α2b剂量组之间重叠。这些重叠的代谢物表明，丙氨酸-丙氨酸和谷氨酸代谢途径、精氨酸和脯氨酸代谢途径的减少以及嘌呤代谢的增加形成了响应IFN-α2b的特征性特征。进一步的剂量相关代谢物表明，不饱和脂肪酸的生物合成仅富含IFN-M和IFN-H，这与针对细菌感染的高度保护有关。外源脂肪酸，尤其是不饱和亚油酸，可以提高斑马鱼感染胞外致病性溶藻弧菌和胞内致病性迟缓爱德华氏菌后的存活能力。这些结果揭示了IFN-α2b保护宿主免受微生物感染的未知机制。我们的研究结果突出了理解IFN在代谢调节内容中的作用的方法。
Interferon (IFN) family is a large group of cytokines involved in innate immune response against various microorganisms. However, whether IFN functions in antimicrobial property by metabolic pathways is largely unknown. In the present study, GC-MS-based metabolome is investigated in humoral fluid of zebrafish (Danio rerio) which are exposed to three doses of IFN-α2b, designed as IFN-L, IFN-M, and IFN-H. Out of 67 compounds identified, 19, 28, and 29 differential abundances of metabolites are identified in the three groups compared with control, respectively. A total of 41 differential metabolites constructed IFN-dependent metabolome, in which 13 overlap among the three doses of IFN-α2b groups. These overlapped metabolites show that decreased alanine asparate and glutamate metabolic pathway, arginine and proline metabolic pathway, and increased purine metabolism form a characteristic feature in response to IFN-α2b. Further dose-related metabolites indicate that biosynthesis of unsaturated fatty acids is enriched only in IFN-M and IFN-H, which is related to high protection against bacterial infection. Exogenous fatty acids, especially unsaturated linoleic acid, may elevate the survival ability of zebrafish infected with extracellular pathogenic V. alginolyticus and intracellular pathogenic Edwardsiella tarda. These results disclose an unknown mechanism by which IFN-α2b protects host from microbial infections. Our findings highlight the ways to understand action of IFN in content of metabolic regulation.