甘露糖
甘露糖受体
巨噬细胞
细胞因子
炎症
下调和上调
体内
细胞内
新陈代谢
生物
化学
体外
细胞生物学
生物化学
免疫学
基因
生物技术
作者
Simone Torretta,Alessandra Scagliola,Luisa Ricci,Francesco Mainini,Sabrina Di Marco,Ivan Cuccovillo,Anna Kajaste‐Rudnitski,David Sumpton,Kevin M. Ryan,Simone Cardaci
标识
DOI:10.1038/s41467-020-20164-6
摘要
D-mannose is a monosaccharide approximately a hundred times less abundant than glucose in human blood. Previous studies demonstrated that supraphysiological levels of D-mannose inhibit tumour growth and stimulate regulatory T cell differentiation. It is not known whether D-mannose metabolism affects the function of non-proliferative cells, such as inflammatory macrophages. Here, we show that D-mannose suppresses LPS-induced macrophage activation by impairing IL-1β production. In vivo, mannose administration improves survival in a mouse model of LPS-induced endotoxemia as well as decreases progression in a mouse model of DSS-induced colitis. Phosphomannose isomerase controls response of LPS-activated macrophages to D-mannose, which impairs glucose metabolism by raising intracellular mannose-6-phosphate levels. Such alterations result in the suppression of succinate-mediated HIF-1α activation, imposing a consequent reduction of LPS-induced Il1b expression. Disclosing an unrecognized metabolic hijack of macrophage activation, our study points towards safe D-mannose utilization as an effective intervention against inflammatory conditions.
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