Cutting Edge: Critical Role of Glycolysis in Human Plasmacytoid Dendritic Cell Antiviral Responses.
Cutting Edge: Critical Role of Glycolysis in Human Plasmacytoid Dendritic Cell Antiviral Responses.
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DOI：
10.4049/jimmunol.1501557
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发表时间：
2016-03-01
期刊：
影响因子：
--
通讯作者：
Gill MA
中科院分区：
文献类型：
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作者：
Bajwa G;DeBerardinis RJ;Shao B;Hall B;Farrar JD;Gill MA
浆细胞样树突状细胞 (pDC) 对于抗病毒防御至关重要，通过分泌高浓度的 IFN-α 来指导免疫反应。这些细胞对于保护肺部免受临床相关呼吸道病毒的侵害至关重要，特别是流感（流感），这是一种导致全球大量发病率和死亡率的病毒。然而，人类如何调节 pDC 对此类病毒病原体的反应却知之甚少。使用基因芯片分析的公正方法，我们发现流感显着影响原代人类 pDC 的代谢。我们证明 Flu 和 RV（另一种常见呼吸道病毒）可诱导 pDC 糖酵解，并且该代谢途径调节 pDC 抗病毒功能，包括 IFN-α 产生和表型成熟。人类志愿者鼻内接种活流感病毒也会增加循环 pDC 中的糖酵解，这凸显了代谢在调节 pDC 对人类病毒感染的免疫反应中先前未被认识到的潜在作用。
Plasmacytoid dendritic cells (pDCs) are vital to antiviral defense, directing immune responses via secretion of huge concentrations of IFN-α. These cells are critical in protecting the lung against clinically relevant respiratory viruses, particularly influenza (Flu), a virus responsible for substantial worldwide morbidity and mortality. How pDC responses to such viral pathogens are regulated, however, is poorly understood in humans. Using an unbiased approach of gene chip analysis, we discovered that Flu significantly impacts metabolism in primary human pDCs. We demonstrate that Flu and RV, another common respiratory virus, induce glycolysis in pDCs and that this metabolic pathway regulates pDC antiviral functions including IFN-α production and phenotypic maturation. Intranasal vaccination of human volunteers with live influenza virus also increases glycolysis in circulating pDCs, highlighting a previously unrecognized potential role for metabolism in regulating pDC immune responses to viral infections in humans.