Glucose Homeostasis Is Important for Immune Cell Viability during Candida Challenge and Host Survival of Systemic Fungal Infection.
Glucose Homeostasis Is Important for Immune Cell Viability during Candida Challenge and Host Survival of Systemic Fungal Infection.
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DOI：
10.1016/j.cmet.2018.03.019
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发表时间：
2018-05-01
期刊：
影响因子：
29
通讯作者：
Traven A
中科院分区：
文献类型：
--
作者：
Tucey TM;Verma J;Harrison PF;Snelgrove SL;Lo TL;Scherer AK;Barugahare AA;Powell DR;Wheeler RT;Hickey MJ;Beilharz TH;Naderer T;Traven A
为了对抗感染，巨噬细胞经历代谢转变，从而增加糖酵解为抗菌炎症和杀死病原体提供燃料。在这里，我们证明了病原体白色念珠菌将这种代谢重编程变成了巨噬细胞的致命弱点。在噬菌体-巨噬细胞相互作用期间，发生相互交织的代谢变化，伴随着宿主和病原体中糖酵解的上调，从而建立葡萄糖竞争。念珠菌在多种碳源上茁壮成长，但受感染的巨噬细胞在代谢上被困在糖酵解中，并依赖于葡萄糖的生存能力：念珠菌通过消耗葡萄糖来利用这一限制，引发快速的巨噬细胞死亡。利用药理学或遗传学手段调节宿主和/或病原体的葡萄糖代谢，我们在小鼠念珠菌血症模型中显示念珠菌感染扰乱宿主葡萄糖稳态，并证明葡萄糖补充剂改善宿主结局。我们的研究结果支持维持葡萄糖稳态的重要性，免疫细胞生存期间念珠菌的挑战和宿主生存系统感染。葡萄糖是先天免疫细胞产生有效抗真菌反应所必需的。Tucey等人表明，对于受感染的巨噬细胞，对葡萄糖的依赖成为它们的垮台：人类真菌病原体白色念珠菌迅速消耗葡萄糖，导致巨噬细胞死亡。在小鼠中，维持宿主葡萄糖稳态对于预防危及生命的真菌感染很重要。
To fight infections, macrophages undergo a metabolic shift whereby increased glycolysis fuels antimicrobial inflammation and killing of pathogens. Here we demonstrate that the pathogen Candida albicans turns this metabolic reprogramming into an Achilles’ heel for macrophages. During Candida-macrophage interactions intertwined metabolic shifts occur, with concomitant upregulation of glycolysis in both host and pathogen setting up glucose competition. Candida thrives on multiple carbon sources, but infected macrophages are metabolically trapped in glycolysis and depend on glucose for viability: Candida exploits this limitation by depleting glucose, triggering rapid macrophage death. Using pharma-cological or genetic means to modulate glucose metabolism of host and/or pathogen, we show that Candida infection perturbs host glucose homeostasis in the murine candidemia model and demonstrate that glucose supplementation improves host out-comes. Our results support the importance of maintaining glucose homeostasis for immune cell survival during Candida challenge and for host survival in systemic infection. Glucose is essential for innate immune cells to mount effective anti-fungal responses. Tucey et al. show that, for infected macrophages, dependence on glucose becomes their downfall: the human fungal pathogen Candida albicans rapidly consumes glucose, causing macrophages to die. In mice, maintaining host glucose homeostasis is important to prevent life-threatening fungal infection.
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影响因子：
3.4
作者：
Barelle CJ;Priest CL;Maccallum DM;Gow NA;Odds FC;Brown AJ
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Brown AJ
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影响因子：
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作者：
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