Innate immune cells such as macrophages and neutrophils initiate protective inflammatory responses and engage antimicrobial responses to provide frontline defence against invading pathogens. These cells can both restrict the availability of certain transition metals that are essential for microbial growth and direct toxic concentrations of metals towards pathogens as antimicrobial responses. Zinc is important for the structure and function of many proteins, however excess zinc can be cytotoxic. In recent years, several studies have revealed that innate immune cells can deliver toxic concentrations of zinc to intracellular pathogens. In this review, we discuss the importance of zinc status during infectious disease and the evidence for zinc intoxication as an innate immune antimicrobial response. Evidence for pathogen subversion of this response is also examined. The likely mechanisms, including the involvement of specific zinc transporters that facilitate delivery of zinc by innate immune cells for metal ion poisoning of pathogens are also considered. Precise mechanisms by which excess levels of zinc can be toxic to microorganisms are then discussed, particularly in the context of synergy with other antimicrobial responses. Finally, we highlight key unanswered questions in this emerging field, which may offer new opportunities for exploiting innate immune responses for anti‐infective development.

中文翻译：

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锌和先天免疫的合金：激发宿主防御感染

巨噬细胞和中性粒细胞等先天免疫细胞启动保护性炎症反应并参与抗菌反应，以提供针对入侵病原体的前线防御。这些细胞既可以限制微生物生长所必需的某些过渡金属的可用性，也可以将有毒浓度的金属直接引向病原体作为抗菌反应。锌对许多蛋白质的结构和功能很重要，但过量的锌可能具有细胞毒性。近年来，多项研究表明，先天免疫细胞可以向细胞内病原体输送有毒浓度的锌。在这篇综述中，我们讨论了感染性疾病期间锌状态的重要性，以及锌中毒作为先天免疫抗菌反应的证据。还检查了这种反应的病原体破坏的证据。还考虑了可能的机制，包括特定锌转运蛋白的参与，这些转运蛋白促进先天免疫细胞为病原体的金属离子中毒而递送锌。然后讨论了过量锌对微生物产生毒性的精确机制，特别是在与其他抗菌反应协同作用的情况下。最后，我们强调了这个新兴领域中未解决的关键问题，这可能为利用先天免疫反应进行抗感染发展提供新的机会。然后讨论了过量锌对微生物产生毒性的精确机制，特别是在与其他抗菌反应协同作用的情况下。最后，我们强调了这个新兴领域中未解决的关键问题，这可能为利用先天免疫反应进行抗感染发展提供新的机会。然后讨论了过量锌对微生物产生毒性的精确机制，特别是在与其他抗菌反应协同作用的情况下。最后，我们强调了这个新兴领域中未解决的关键问题，这可能为利用先天免疫反应进行抗感染发展提供新的机会。