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The battle for iron in enteric infections.
Immunology ( IF 4.9 ) Pub Date : 2020-07-08 , DOI: 10.1111/imm.13236
Ana Sousa Gerós 1, 2 , Alison Simmons 1, 2 , Hal Drakesmith 1 , Anna Aulicino 1, 2 , Joe N Frost 1
Affiliation  

Iron is an essential element for almost all living organisms, but can be extremely toxic in high concentrations. All organisms must therefore employ homeostatic mechanisms to finely regulate iron uptake, usage and storage in the face of dynamic environmental conditions. The critical step in mammalian systemic iron homeostasis is the fine regulation of dietary iron absorption. However, as the gastrointestinal system is also home to >1014 bacteria, all of which engage in their own programmes of iron homeostasis, the gut represents an anatomical location where the inter‐kingdom fight for iron is never‐ending. Here, we explore the molecular mechanisms of, and interactions between, host and bacterial iron homeostasis in the gastrointestinal tract. We first detail how mammalian systemic and cellular iron homeostasis influences gastrointestinal iron availability. We then focus on two important human pathogens, Salmonella and Clostridia; despite their differences, they exemplify how a bacterial pathogen must navigate and exploit this web of iron homeostasis interactions to avoid host nutritional immunity and replicate successfully. We then reciprocally explore how iron availability interacts with the gastrointestinal microbiota, and the consequences of this on mammalian physiology and pathogen iron acquisition. Finally, we address how understanding the battle for iron in the gastrointestinal tract might inform clinical practice and inspire new treatments for important diseases.

中文翻译:

肠道感染中铁的争夺战。

铁是几乎所有生物体的必需元素,但高浓度时可能具有剧毒。因此,面对动态环境条件,所有生物体都必须采用稳态机制来精细调节铁的吸收、使用和储存。哺乳动物全身铁稳态的关键步骤是膳食铁吸收的精细调节。然而,由于胃肠道系统也是超过 10 14 个细菌的家园,所有这些细菌都参与自己的铁稳态程序,因此肠道代表了一个解剖位置,在该位置上,不同王国之间对铁的争夺永无止境。在这里,我们探索胃肠道中宿主和细菌铁稳态的分子机制以及它们之间的相互作用。我们首先详细介绍哺乳动物的全身和细胞铁稳态如何影响胃肠道铁的可用性。然后我们重点关注两种重要的人类病原体:沙门氏菌梭状芽胞杆菌;尽管存在差异,但它们举例说明了细菌病原体必须如何导航和利用铁稳态相互作用的网络来避免宿主的营养免疫并成功复制。然后,我们相互探讨铁的可用性如何与胃肠道微生物群相互作用,以及这对哺乳动物生理学和病原体铁获取的影响。最后,我们讨论了了解胃肠道中铁的斗争如何为临床实践提供信息并激发重要疾病的新治疗方法。
更新日期:2020-07-08
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