Coordination of the Uptake and Metabolism of Amino Acids in Mycobacterium tuberculosis-Infected Macrophages.
Coordination of the Uptake and Metabolism of Amino Acids in Mycobacterium tuberculosis-Infected Macrophages.
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结核分枝杆菌感染的巨噬细胞中氨基酸的摄取和代谢的协调。
DOI：
10.3389/fimmu.2021.711462
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发表时间：
2021
影响因子：
7.3
通讯作者：
Shi L
中科院分区：
文献类型：
--
作者：
Jiang Q;Shi L
巨噬细胞极化为M1样表型，这对于巨噬细胞对抗细胞内病原体的促炎和抗微生物反应至关重要，与代谢重编程至瓦尔堡效应和来自NOS 2表达增加的NO高输出相关。然而，在M1极化过程中对其他氨基酸的摄取和代谢的了解有限。基于一组上调的转运蛋白和酶参与结核分枝杆菌感染的巨噬细胞中氨基酸的摄取和/或代谢的功能分析，加上免疫细胞活化的研究，我们假设一个连贯的方案，在巨噬细胞极化M1样表型的氨基酸摄取和代谢。我们描述了潜在的机制，增加精氨酸代谢的NOS 2代谢耦合系统L转运蛋白LAT1和LAT2的中性氨基酸的摄取，包括那些驱动mTORC 1信号向M1样表型。我们还讨论了谷氨酰胺代谢在M1样巨噬细胞代谢重编程中的多效性作用。总的来说，我们的分析认为，协调的氨基酸摄取和代谢构成了广泛的代谢计划所需的巨噬细胞极化M1样表型对M的一个组成部分。肺结核感染。这一想法可能会刺激未来的实验努力，以阐明巨噬细胞活化的代谢图，用于抗结核治疗的发展。
Macrophage polarization to the M1-like phenotype, which is critical for the pro-inflammatory and antimicrobial responses of macrophages against intracellular pathogens, is associated with metabolic reprogramming to the Warburg effect and a high output of NO from increased expression of NOS2. However, there is limited understanding about the uptake and metabolism of other amino acids during M1 polarization. Based on functional analysis of a group of upregulated transporters and enzymes involved in the uptake and/or metabolism of amino acids in Mycobacterium tuberculosis-infected macrophages, plus studies of immune cell activation, we postulate a coherent scheme for amino acid uptake and metabolism during macrophage polarization to the M1-like phenotype. We describe potential mechanisms that the increased arginine metabolism by NOS2 is metabolically coupled with system L transporters LAT1 and LAT2 for the uptake of neutral amino acids, including those that drive mTORC1 signaling toward the M1-like phenotype. We also discuss the underappreciated pleiotropic roles of glutamine metabolism in the metabolic reprogramming of M1-like macrophages. Collectively, our analyses argue that a coordinated amino acid uptake and metabolism constitutes an integral component of the broad metabolic scheme required for macrophage polarization to M1-like phenotype against M. tuberculosis infection. This idea could stimulate future experimental efforts to elucidate the metabolic map of macrophage activation for the development of anti-tuberculosis therapies.
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阳离子氨基酸转运蛋白2增强了幽门螺杆菌感染期间的先天免疫力。
影响因子：
3.7
作者：
Barry DP;Asim M;Scull BP;Piazuelo MB;de Sablet T;Lewis ND;Coburn LA;Singh K;Ellies LG;Gobert AP;Chaturvedi R;Wilson KT
通讯作者：
Wilson KT
影响因子：
7.3
作者：
Lange SM;McKell MC;Schmidt SM;Hossfeld AP;Chaturvedi V;Kinder JM;McAlees JW;Lewkowich IP;Way SS;Turner J;Qualls JE
通讯作者：
Qualls JE
影响因子：
8.4
作者：
Koo, Mi-Sun;Subbian, Selvakumar;Kaplan, Gilla
通讯作者：
Kaplan, Gilla
影响因子：
5.7
作者：
Gross, Matt I.;Demo, Susan D.;Bennett, Mark K.
通讯作者：
Bennett, Mark K.
影响因子：
8.8
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
通讯作者：
Sheedy FJ