Mycobacterium tuberculosis Limits Host Glycolysis and IL-1β by Restriction of PFK-M via MicroRNA-21.
Mycobacterium tuberculosis Limits Host Glycolysis and IL-1β by Restriction of PFK-M via MicroRNA-21.
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DOI：
10.1016/j.celrep.2019.12.015
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发表时间：
2020-01-07
期刊：
影响因子：
8.8
通讯作者：
Sheedy FJ
中科院分区：
文献类型：
--
作者：
Hackett EE;Charles-Messance H;O'Leary SM;Gleeson LE;Muñoz-Wolf N;Case S;Wedderburn A;Johnston DGW;Williams MA;Smyth A;Ouimet M;Moore KJ;Lavelle EC;Corr SC;Gordon SV;Keane J;Sheedy FJ
糖酵解代谢的增加最近成为驱动宿主防御结核分枝杆菌（Mtb）的一个重要过程，但很少有人知道这个过程是如何在感染过程中进行调节的。在这里，我们观察到宿主糖酵解在结核分枝杆菌感染的巨噬细胞，这是依赖于持续上调的抗炎microRNA-21（miR-21）的增殖分枝杆菌的抑制。miR-21对糖酵解的抑制是通过在糖酵解的关键步骤靶向磷酸果糖激酶，肌肉亚型（PFK-m）介导的，其通过限制促炎介质（主要是IL-1β）促进细菌生长。与其他糖酵解基因不同，PFK-m的表达和活性在Mtb感染期间通过miR-21介导的调节受到抑制，而其他活性较低的同工酶占主导地位。值得注意的是，驱动Mtb宿主防御的IFNγ抑制miR-21表达，迫使PFK复合物中的同工酶转换，增加PFK-m表达和巨噬细胞糖酵解。这些发现将miR-21靶向PFK-m作为控制巨噬细胞免疫代谢功能的关键节点。
Increased glycolytic metabolism recently emerged as an essential process driving host defence against Mycobacterium tuberculosis (Mtb), but little is known about how this process is regulated during infection. Here, we observe repression of host glycolysis in Mtb-infected macrophages, which was dependent on sustained up-regulation of the anti-inflammatory microRNA-21 (miR-21) by proliferating mycobacteria. The dampening of glycolysis by miR-21 was mediated through targeting of phospho-fructo-kinase, muscle isoform (PFK-m) at the committed step of glycolysis, which facilitated bacterial growth by limiting pro-inflammatory mediators, chiefly IL-1β. Unlike other glycolytic genes, PFK-m expression and activity is repressed during Mtb infection through miR-21-mediated regulation, while other less active isoenzymes dominate. Notably, IFNγ, which drives Mtb host defence, inhibits miR-21 expression, forcing an isoenzyme switch in the PFK-complex, augmenting PFK-m expression and macrophage glycolysis. These findings place targeting of PFK-m by miR-21 as a key node controlling macrophage immunometabolic function.
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DOI：
10.1126/science.1224026
发表时间：
2012-09-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
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Casanova JL
影响因子：
28.3
作者：
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通讯作者：
Stienstra, Rinke
DOI：
10.1084/jem.20172020
发表时间：
2018-04-02
期刊：
The Journal of experimental medicine
影响因子：
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作者：
Huang L;Nazarova EV;Tan S;Liu Y;Russell DG
通讯作者：
Russell DG
影响因子：
6.8
作者：
Egorova N;Cumming T;Shirbin C;Veldsman M;Werden E;Brodtmann A
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Brodtmann A
影响因子：
4.3
作者：
Hobson-Gutierrez SA;Carmona-Fontaine C
通讯作者：
Carmona-Fontaine C