Marra Alice, Masson Florent, Lemaitre Bruno
Global Health Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Microlife. 2021 Jun 25;2:uqab008. doi: 10.1093/femsml/uqab008. eCollection 2021.
Iron is involved in numerous biological processes in both prokaryotes and eukaryotes and is therefore subject to a tug-of-war between host and microbes upon pathogenic infections. In the fruit fly , the iron transporter Transferrin 1 (Tsf1) mediates iron relocation from the hemolymph to the fat body upon infection as part of the nutritional immune response. The sequestration of iron in the fat body renders it less available for pathogens, hence limiting their proliferation and enhancing the host ability to fight the infection. Here we investigate the interaction between host iron homeostasis and , a facultative, vertically transmitted, endosymbiont of . This low-pathogenicity bacterium is devoid of cell wall and is able to thrive in the host hemolymph without triggering pathogen-responsive canonical immune pathways. However, hemolymph proteomics revealed an enrichment of Tsf1 in infected flies. We find that induces expression and triggers an iron sequestration response similarly to pathogenic bacteria. We next demonstrate that free iron cannot be used by while Tsf1-bound iron promotes bacterial growth, underlining the adaptation of to the intra-host lifestyle where iron is mostly protein-bound. Our results show that Tsf1 is used both by the fly to sequester iron and by to forage host iron, making it a central protein in endosymbiotic homeostasis.
铁参与原核生物和真核生物的众多生物过程，因此在病原体感染时会在宿主和微生物之间展开争夺。在果蝇中，铁转运蛋白转铁蛋白1（Tsf1）在感染时介导铁从血淋巴转移至脂肪体，作为营养免疫反应的一部分。铁在脂肪体中的隔离使其对病原体的可用性降低，从而限制病原体的增殖并增强宿主对抗感染的能力。在此，我们研究宿主铁稳态与果蝇沃尔巴克氏体（Wolbachia）之间的相互作用，果蝇沃尔巴克氏体是果蝇的一种兼性、垂直传播的内共生菌。这种低致病性细菌没有细胞壁，能够在宿主血淋巴中生存而不触发病原体反应性经典免疫途径。然而，血淋巴蛋白质组学显示感染果蝇中Tsf1富集。我们发现果蝇沃尔巴克氏体诱导Tsf1表达并引发与病原菌类似的铁隔离反应。接下来我们证明游离铁不能被果蝇沃尔巴克氏体利用，而与Tsf1结合的铁则促进细菌生长，这突出了果蝇沃尔巴克氏体对宿主内铁主要与蛋白质结合的生活方式的适应性。我们的结果表明，Tsf1既被果蝇用于隔离铁，也被果蝇沃尔巴克氏体用于获取宿主铁，使其成为内共生稳态中的核心蛋白。
