Candida albicans Modulates Host Defense by Biosynthesizing the Pro-Resolving Mediator Resolvin E1
Candida albicans Modulates Host Defense by Biosynthesizing the Pro-Resolving Mediator Resolvin E1
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DOI：
10.1371/journal.pone.0001316
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发表时间：
2007-12-19
期刊：
影响因子：
3.7
通讯作者：
Agabian, Nina
中科院分区：
文献类型：
--
作者：
Haas-Stapleton, Eric J.;Lu, Yan;Agabian, Nina
白色念珠菌是人类的一种机会致病性真菌病原体，其寄生在上皮表面上，但当致病时可引起炎症。消退素是一类来源于ω-3多不饱和脂肪酸（PUFA）的抗炎脂质，其在炎症消退阶段期间减弱中性粒细胞迁移。在本报告中，我们证明了C。白色念珠菌生物合成与人类细胞产生的消退素化学上相同的消退素。与人Resolvin E1（RvE 1）的跨细胞生物合成相反，RvE 1在C.白色念珠菌在没有其他细胞伴侣的情况下发生。C. RvE 1的生物合成对脂氧合酶和细胞色素P450单加氧酶抑制剂敏感。我们发现，10 nM RvE 1减少中性粒细胞对IL-8的趋化反应; 1 nM RvE 1增强人类中性粒细胞对念珠菌的吞噬作用，以及细胞内ROS的产生和杀伤，同时对中性粒细胞运动没有直接影响。在系统性念珠菌病的小鼠模型中，RvE 1刺激了真菌从循环血液中的清除。这些结果揭示了一个种间化学信号系统，调节宿主的免疫功能，并可能在平衡宿主携带的寄生虫和致病性C。白色念珠菌。
Candida albicans is an opportunistic fungal pathogen of humans that resides commensally on epithelial surfaces, but can cause inflammation when pathogenic. Resolvins are a class of anti-inflammatory lipids derived from omega-3 polyunsaturated fatty acids (PUFA) that attenuate neutrophil migration during the resolution phase of inflammation. In this report we demonstrate that C. albicans biosynthesizes resolvins that are chemically identical to those produced by human cells. In contrast to the trans-cellular biosynthesis of human Resolvin E1 (RvE1), RvE1 biosynthesis in C. albicans occurs in the absence of other cellular partners. C. albicans biosynthesis of RvE1 is sensitive to lipoxygenase and cytochrome P450 monoxygenase inhibitors. We show that 10nM RvE1 reduces neutrophil chemotaxis in response to IL-8; 1nM RvE1 enhanced phagocytosis of Candida by human neutrophils, as well as intracellular ROS generation and killing, while having no direct affect on neutrophil motility. In a mouse model of systemic candidiasis, RvE1 stimulated clearance of the fungus from circulating blood. These results reveal an inter-species chemical signaling system that modulates host immune functions and may play a role in balancing host carriage of commensal and pathogenic C. albicans.