Temporal modulation of host aerobic glycolysis determines the outcome of Mycobacterium marinum infection.
Temporal modulation of host aerobic glycolysis determines the outcome of Mycobacterium marinum infection.
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宿主有氧糖酵解的时间调节决定了海分枝杆菌感染的结果。
DOI：
10.1016/j.fsi.2019.11.051
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发表时间：
2019-11
期刊：
影响因子：
--
通讯作者：
Niu Chen
中科院分区：
文献类型：
--
作者：
Kan Yuanqing;Meng Lu;Xie Lingling;Liu Lixia;Dong Wenyue;Feng Jintao;Yan Yuchen;Zhao Chao;Peng Gang;Wang Decheng;Lu Mingfang;Yang Chen;Niu Chen
Macrophages are the first-line host defense that the invading Mycobacterium tuberculosis (Mtb) encounters. It has been recently reported that host aerobic glycolysis was elevated post the infection by a couple of virulent mycobacterial species. However, whether this metabolic transition is required for host defense against intracellular pathogens and the underlying mechanisms remain to be further investigated. A pathogenic mycobacterial species,M. marinum, is genetically close to Mtb and was utilized in this study. Through analyzing cellular carbon metabolism of RAW 264.7 (a murine macrophage-like cell line) postM. marinuminfection, a strong elevation of glycolysis was observed. Next, three glycolysis inhibitors were examined for their ability to inhibit mycobacterial proliferation inside RAW264.7 macrophages. Among them, a glucose analog, 2-deoxyglucose (2-DG) displayed a protective role against mycobacterial infection. Treatment with 2-DG at concentrations of 0.5 or 1 mM significantly induced autophagy and decreased the phagocytosis ofM. marinumby macrophages. Moreover, 2-DG pre-treatment exerted a significantly protective effect on zebrafish larvae by limiting the proliferation ofM. marinum, and such effect was correlated to tumor necrosis factor alpha (TNF-α) as the 2-DG pre-treatment increased the expression of TNF-α in both mouse peritoneal macrophages and zebrafish. On the contrary, the 2-DG treatment post infection did not restrain proliferation ofM. marinumin WT zebrafish, and even accelerated bacterial replication in TNF-α−/−zebrafish. Together, modulation of glycolysis prior to infection boosts host immunity againstM. marinuminfection, indicating a potential intervention strategy to control mycobacterial infection.
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影响因子：
--
作者：
van der Vaart M;Spaink HP;Meijer AH
通讯作者：
Meijer AH
影响因子：
2
作者：
Mason T;Snell K;Mittge E;Melancon E;Montgomery R;McFadden M;Camoriano J;Kent ML;Whipps CM;Peirce J
通讯作者：
Peirce J
影响因子：
5.2
作者：
Du P;Sohaskey CD;Shi L
通讯作者：
Shi L
影响因子：
64.5
作者：
Chang CH;Curtis JD;Maggi LB Jr;Faubert B;Villarino AV;O'Sullivan D;Huang SC;van der Windt GJ;Blagih J;Qiu J;Weber JD;Pearce EJ;Jones RG;Pearce EL
通讯作者：
Pearce EL
影响因子：
9.1
作者：
Mortaz, Esmaeil;Adcock, Ian M.;Tabarsi, Payam;Masjedi, Mohammad Reza;Mansouri, Davood;Velayati, Ali Akbar;Casanova, Jean-Laurent;Barnes, Peter J.
通讯作者：
Barnes, Peter J.