The iron-infection axis revisited: From mechanistic insights to therapeutic frontiers

IF 1.5 4区医学 Q3 INFECTIOUS DISEASES

Journal of Infection and Chemotherapy Pub Date : 2025-09-25 DOI:10.1016/j.jiac.2025.102818

Hiroshi Moro

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Abstract

Iron is an essential element for both the host and the invading pathogens since its chemically reactive nature makes it favorable for its nutritional value during infection. Pathogens employ high-affinity siderophores to acquire iron. Meanwhile the host sequestrates iron by binding proteins and a suite of regulatory factors including hepcidin, lipocalin-2, and natural resistance-associated macrophage protein 1. These natural immune responses by the host are intimately linked with the inflammatory mechanisms to control infection by restricting access to iron to the pathogen. In the era of increasing antimicrobial resistance, this interplay presents an attractive target for novel drug development, which has led to the clinical use of siderophore-conjugated antimicrobials. This comprehensive overview of the host-pathogen iron interplay, highlighting the dynamics of Iron-infection Axis offers a new paradigm for understanding disease pathogenesis. A deeper appreciation of this axis is expected to accelerate the development of future diagnostic and therapeutic strategies.

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铁感染轴重访：从机械洞察到治疗前沿

铁是宿主和入侵病原体的必需元素，因为它的化学反应性质使其在感染期间具有有利的营养价值。病原体利用高亲和力的铁载体获取铁。同时，宿主通过结合蛋白和一系列调节因子（包括hepcidin、lipocalin-2和天然耐药相关巨噬细胞蛋白1）来隔离铁。宿主的这些自然免疫反应与炎症机制密切相关，通过限制病原体获得铁来控制感染。在抗菌素耐药性日益增加的时代，这种相互作用为新药开发提供了一个有吸引力的目标，这导致了铁载体偶联抗菌素的临床使用。本文全面概述了宿主-病原体铁相互作用，强调了铁感染轴的动力学，为理解疾病发病机制提供了新的范式。对这一轴的深入了解有望加速未来诊断和治疗策略的发展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Infection and Chemotherapy INFECTIOUS DISEASES-PHARMACOLOGY & PHARMACY

CiteScore

4.10

自引率

4.50%

发文量

303

审稿时长

47 days

期刊介绍： The Journal of Infection and Chemotherapy (JIC) — official journal of the Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases — welcomes original papers, laboratory or clinical, as well as case reports, notes, committee reports, surveillance and guidelines from all parts of the world on all aspects of chemotherapy, covering the pathogenesis, diagnosis, treatment, and control of infection, including treatment with anticancer drugs. Experimental studies on animal models and pharmacokinetics, and reports on epidemiology and clinical trials are particularly welcome.