Agoro Rafiou, Mura Catherine
Medical and Molecular Genetics, Indiana University, School of Medicine, Indianapolis, IN 46202, USA.
Experimental and Molecular Immunology and Neurogenetics (INEM), Mixed Research Unit UMR7355, National Center for Scientific Research and Orléans University, 45071 Orléans, France.
Pharmaceuticals (Basel). 2019 May 17;12(2):75. doi: 10.3390/ph12020075.
Iron is an essential element that is required for oxygen transfer, redox, and metabolic activities in mammals and bacteria. Mycobacteria, some of the most prevalent infectious agents in the world, require iron as growth factor. Mycobacterial-infected hosts set up a series of defense mechanisms, including systemic iron restriction and cellular iron distribution, whereas mycobacteria have developed sophisticated strategies to acquire iron from their hosts and to protect themselves from iron's harmful effects. Therefore, it is assumed that host iron and iron-binding proteins, and natural or synthetic chelators would be keys targets to inhibit mycobacterial proliferation and may have a therapeutic potential. Beyond this hypothesis, recent evidence indicates a host protective effect of iron against mycobacterial infections likely through promoting remodeled immune response. In this review, we discuss experimental procedures and clinical observations that highlight the role of the immune response against mycobacteria under various iron availability conditions. In addition, we discuss the clinical relevance of our knowledge regarding host susceptibility to mycobacteria in the context of iron availability and suggest future directions for research on the relationship between host iron and the immune response and the use of iron as a therapeutic agent.
铁是一种必需元素，在哺乳动物和细菌的氧气转运、氧化还原及代谢活动中不可或缺。分枝杆菌是世界上一些最常见的感染病原体，需要铁作为生长因子。感染分枝杆菌的宿主会建立一系列防御机制，包括全身性铁限制和细胞内铁分布，而分枝杆菌则已形成复杂的策略，从宿主获取铁并保护自身免受铁的有害影响。因此，人们认为宿主铁、铁结合蛋白以及天然或合成螯合剂将是抑制分枝杆菌增殖的关键靶点，可能具有治疗潜力。除了这一假设外，最近的证据表明铁可能通过促进重塑的免疫反应对分枝杆菌感染产生宿主保护作用。在这篇综述中，我们讨论了突出不同铁可利用性条件下针对分枝杆菌免疫反应作用的实验程序和临床观察结果。此外，我们讨论了在铁可利用性背景下关于宿主对分枝杆菌易感性的知识的临床相关性，并提出了关于宿主铁与免疫反应关系以及将铁用作治疗剂研究的未来方向。
