Relevance of the Warburg Effect in Tuberculosis for Host-Directed Therapy.
Relevance of the Warburg Effect in Tuberculosis for Host-Directed Therapy.
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DOI：
10.3389/fcimb.2020.576596
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发表时间：
2020
影响因子：
5.7
通讯作者：
Steyn AJC
中科院分区：
文献类型：
--
作者：
Cumming BM;Pacl HT;Steyn AJC
2019年，结核病造成的死亡人数超过任何其他传染病。多种药物耐药性和艾滋病毒合并感染的持续发展加剧了这一流行病。因此，最近的研究侧重于确定可与抗分枝杆菌药物联合使用的宿主定向疗法（HDTs），以缩短结核病治疗时间并改善结核病结局。在寻找有效的HDTs治疗结核病的过程中，研究着眼于免疫代谢，研究代谢在宿主免疫中的作用，特别是Warburg效应。在从体外系统到临床的各种实验范式中，关于Warburg效应在结核病中的作用的研究产生了看似相互矛盾的结果和矛盾的结论。为了调和这些文献，我们采用历史方法重新审视Warburg效应的定义，重新检查癌症领域关于Warburg效应的基础论文，并探索其在免疫代谢中的应用。在确定的背景下，我们评估了研究结核病代谢和免疫代谢的文献，以获得足够的证据来支持Warburg效应在结核病免疫中的作用。强调了动物模型、巨噬细胞来源种类、感染持续时间和用于这些研究的结核分枝杆菌菌株之间差异的影响。此外，还讨论了使用2-脱氧葡萄糖作为糖酵解抑制剂的缺点。最后，我们提出了一些实验标准，这些标准对未来研究结核病中的Warburg效应至关重要，有助于高强度结核病防治研究。
Tuberculosis (TB) was responsible for more deaths in 2019 than any other infectious agent. This epidemic is exacerbated by the ongoing development of multi-drug resistance and HIV co-infection. Recent studies have therefore focused on identifying host-directed therapies (HDTs) that can be used in combination with anti-mycobacterial drugs to shorten the duration of TB treatment and improve TB outcomes. In searching for effective HDTs for TB, studies have looked toward immunometabolism, the study of the role of metabolism in host immunity and, in particular, the Warburg effect. Across a variety of experimental paradigms ranging from in vitro systems to the clinic, studies on the role of the Warburg effect in TB have produced seemingly conflicting results and contradictory conclusions. To reconcile this literature, we take a historical approach to revisit the definition of the Warburg effect, re-examine the foundational papers on the Warburg effect in the cancer field and explore its application to immunometabolism. With a firm context established, we assess the literature investigating metabolism and immunometabolism in TB for sufficient evidence to support the role of the Warburg effect in TB immunity. The effects of the differences between animal models, species of origin of the macrophages, duration of infection and Mycobacterium tuberculosis strains used for these studies are highlighted. In addition, the shortcomings of using 2-deoxyglucose as an inhibitor of glycolysis are discussed. We conclude by proposing experimental criteria that are essential for future studies on the Warburg effect in TB to assist with the research for HDTs to combat TB.
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影响因子：
29
作者：
Corbet, Cyril;Pinto, Adan;Feron, Olivier
通讯作者：
Feron, Olivier
影响因子：
5.9
作者：
Epstein T;Xu L;Gillies RJ;Gatenby RA
通讯作者：
Gatenby RA
影响因子：
7.7
作者：
Cumming BM;Addicott KW;Adamson JH;Steyn AJ
通讯作者：
Steyn AJ
影响因子：
37.3
作者：
Fan TW;Lane AN;Higashi RM;Farag MA;Gao H;Bousamra M;Miller DM
通讯作者：
Miller DM
影响因子：
4.3
作者：
Danhier, Pierre;Banski, Piotr;Porporato, Paolo E.
通讯作者：
Porporato, Paolo E.