Mycobacteria, metals, and the macrophage.
Mycobacteria, metals, and the macrophage.
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DOI：
10.1111/imr.12265
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发表时间：
2015-03
影响因子：
8.7
通讯作者：
Niederweis M
中科院分区：
文献类型：
--
作者：
Neyrolles O;Wolschendorf F;Mitra A;Niederweis M
结核分枝杆菌是一种兼性细胞内病原体，在宿主巨噬细胞内繁殖。M.结核病是利用和操纵感染的巨噬细胞内的金属阳离子运输，以确保吞噬体内的存活和复制。在这里，我们描述了最近的迷人的发现，哺乳动物的免疫系统响应感染与M。通过使吞噬体中的铜和锌超载来治疗结核病，这两种金属是少量的必需营养素，但过量则有毒。M.结核病已经发展了多方面的抗性机制以保护自身免受金属毒性，包括控制摄取、在细胞内隔离、氧化和流出。宿主对感染的反应将这种金属中毒策略与剥夺M.结核病从金属，如铁和锰，以防止细菌复制。这两种免疫机制都依赖于吞噬体成熟过程中金属转运蛋白向吞噬体膜的转运。这篇综述总结了这些最新的研究结果，并讨论了金属靶向方法如何补充现有的结核病化疗方案与新的抗感染治疗。
Mycobacterium tuberculosis is a facultative intracellular pathogen that thrives inside host macrophages. A key trait of M. tuberculosis is to exploit and manipulate metal cation trafficking inside infected macrophages to ensure survival and replication inside the phagosome. Here we describe the recent fascinating discoveries that the mammalian immune system responds to infections with M. tuberculosis by overloading the phagosome with copper and zinc, two metals which are essential nutrients in small quantities but are toxic in excess. M. tuberculosis has developed multi-faceted resistance mechanisms to protect itself from metal toxicity including control of uptake, sequestration inside the cell, oxidation, and efflux. The host response to infections combines this metal poisoning strategy with nutritional immunity mechanisms that deprive M. tuberculosis from metals such as iron and manganese to prevent bacterial replication. Both immune mechanisms rely on the translocation of metal transporter proteins to the phagosomal membrane during the maturation process of the phagosome. This review summarizes these recent findings and discusses how metal-targeted approaches might complement existing TB chemotherapeutic regimens with novel anti-infective therapies.