The fatty acid oleate is required for innate immune activation and pathogen defense in Caenorhabditis elegans
The fatty acid oleate is required for innate immune activation and pathogen defense in Caenorhabditis elegans
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DOI：
10.1371/journal.ppat.1007893
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发表时间：
2019-06-01
期刊：
影响因子：
6.7
通讯作者：
Pukkila-Worley, Read
中科院分区：
文献类型：
--
作者：
Anderson, Sarah M.;Cheesman, Hilary K.;Pukkila-Worley, Read
脂肪酸影响许多生理过程，除了形成膜和身体脂肪储存的构建块。在这项研究中，我们发现的作用，单不饱和脂肪酸油酸在先天性免疫反应的线虫秀丽隐杆线虫。通过对天然免疫防御基因调节因子的RNAi筛选，我们鉴定了C.优雅我们发现油酸的合成是病原体介导的免疫防御基因的诱导所必需的。因此，C.缺乏油酸生产的秀丽线虫对多种人类病原体的感染是高度敏感的，这可以通过添加外源性油酸来挽救。然而，油酸不足以驱动保护性免疫激活。总之，这些数据增加了已知的单不饱和脂肪酸的健康促进作用，并建议营养储存，代谢和宿主对细菌感染的易感性之间的古老联系。作者摘要多细胞生物的进化已经形成了它们与病原微生物的相互作用。微线虫C.线虫以细菌为食，并进化出了针对摄入的病原体的诱导性免疫防御，这些免疫防御在肠上皮细胞内协调。C.因此，秀丽隐杆线虫提出了一个遗传系统来表征先天免疫防御激活的要求。在这里，我们表明，单不饱和脂肪酸油酸酯是必要的诱导先天免疫防御和保护免受细菌病原体，这定义了一个新的联系之间的代谢和调节的多细胞动物宿主的抗病原体反应。
Fatty acids affect a number of physiological processes, in addition to forming the building blocks of membranes and body fat stores. In this study, we uncover a role for the monounsaturated fatty acid oleate in the innate immune response of the nematode Caenorhabditis elegans. From an RNAi screen for regulators of innate immune defense genes, we identified the two stearoyl-coenzyme A desaturases that synthesize oleate in C. elegans. We show that the synthesis of oleate is necessary for the pathogen-mediated induction of immune defense genes. Accordingly, C. elegans deficient in oleate production are hypersusceptible to infection with diverse human pathogens, which can be rescued by the addition of exogenous oleate. However, oleate is not sufficient to drive protective immune activation. Together, these data add to the known health-promoting effects of monounsaturated fatty acids, and suggest an ancient link between nutrient stores, metabolism, and host susceptibility to bacterial infection.Author summary The evolution of multicellular organisms has been shaped by their interactions with pathogenic microorganisms. The microscopic nematode C. elegans eats bacteria for food and has evolved inducible immune defenses toward ingested pathogens that are coordinated within intestinal epithelial cells. C. elegans, therefore, presents a genetic system to characterize the requirements for the activation of innate immune defenses. Here, we show that the monounsaturated fatty acid oleate is necessary for the induction of innate immune defenses and for protection against bacterial pathogens, which defines a new link between metabolism and the regulation of anti-pathogen responses in a metazoan host.