Metabolic Reprogramming of Host Cells by Virulent Francisella tularensis for Optimal Replication and Modulation of Inflammation.
Metabolic Reprogramming of Host Cells by Virulent Francisella tularensis for Optimal Replication and Modulation of Inflammation.
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DOI：
10.4049/jimmunol.1502456
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发表时间：
2016-05-15
期刊：
影响因子：
--
通讯作者：
Bosio CM
中科院分区：
文献类型：
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作者：
Wyatt EV;Diaz K;Griffin AJ;Rasmussen JA;Crane DD;Jones BD;Bosio CM
巨噬细胞代谢从氧化磷酸化到有氧糖酵解的转变是激活以有效对抗入侵病原体的必要条件。土拉热弗朗西丝菌是一种兼性胞内细菌，可引起一种称为土拉菌病的急性致命疾病。其毒力的主要机制是其在巨噬细胞的胞质溶胶中复制时逃避和抑制炎症反应的能力。F.土拉热菌调节巨噬细胞活化尚未完全阐明。在这里，我们证明了有毒的F。土拉热通过阻止它们向有氧糖酵解的转变而损害原代巨噬细胞中炎性细胞因子的产生，如通过HIF-1α的下调和pfkfb 3的上调失败所证明的。我们还发现，弗朗西斯菌胶囊是需要这个过程。除了调节炎症反应外，抑制宿主细胞中的糖酵解也是毒性弗朗西斯菌早期复制所需的。总之，我们的数据表明，宿主细胞的代谢重编程的F。土拉热菌是抑制宿主防御机制和细菌复制的关键成分。
A shift in macrophage metabolism from oxidative phosphorylation to aerobic glycolysis is a requirement for activation to effectively combat invading pathogens. Francisella tularensis is a facultative intracellular bacterium that causes an acute, fatal disease called tularemia. Its primary mechanism of virulence is its ability to evade and suppress inflammatory responses while replicating in the cytosol of macrophages. The means by which F. tularensis modulates macrophage activation are not fully elucidated. Here we demonstrate that virulent F. tularensis impairs production of inflammatory cytokines in primary macrophages by preventing their shift to aerobic glycolysis, as evidenced by the down regulation of HIF-1α, and failure to upregulate pfkfb3. We also uncover that Francisella capsule is required for this process. In addition to modulating inflammatory responses, inhibition of glycolysis in host cells is also required for early replication of virulent Francisella. Together our data demonstrate that metabolic reprogramming of host cells by F. tularensis is a key component of both inhibition of host defense mechanisms and replication of the bacterium.