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首页> 外文期刊>Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society >The iron export protein ferroportin 1 is differentially expressed in mouse macrophage populations and is present in the mycobacterial-containing phagosome.
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The iron export protein ferroportin 1 is differentially expressed in mouse macrophage populations and is present in the mycobacterial-containing phagosome.

机译：铁输出蛋白ferroportin 1在小鼠巨噬细胞群体中差异表达，并存在于含分枝杆菌的吞噬体中。

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摘要

Intracellular pathogens, including Mycobacterium tuberculosis, obtain iron from the host for their survival. Ferroportin 1 (FPN1; SLC40A1) is the sole iron exporter from mammalian cells and is expressed in the duodenum and macrophages. In the present study, we show that FPN1 mRNA levels in the mouse macrophage cell line RAW264.7 are synergistically induced by treatment with live or gamma-irradiated M. tuberculosis and IFN-gamma. FPN1 mRNA levels were also induced by Mycobacterium avium and IFN-gamma in RAW264.7 cells and the mouse alveolar macrophage cell line AMJ2-C8. Treatment of mouse resident peritoneal macrophages with M. tuberculosis and IFN-gamma resulted in a sixfold increase in FPN1 mRNA expression. In contrast, M. tuberculosis and IFN-gamma inhibited FPN1 mRNA expression in bone marrow-derived macrophages and lung macrophages, which have high basal levels of FPN1 mRNA expression. Using confocal microscopy, FPN1 protein localized rapidly to M. tuberculosis phagosomes after infection in RAW264.7 macrophages. In RAW264.7 cells expressing wild-type natural resistance-associated macrophage protein 1 (Nramp1(Gly169)), FPN1 and Nramp1 partially colocalized in late endosomes/lysosomes prior to infection. After 2 h of infection, Nramp1 and FPN1 were present in M. tuberculosis phagosomes. Our studies provide evidence for transcriptional regulation of FPN1 by pathogenic mycobacteria and IFN-gamma, which is dependent on the macrophage type. The trafficking of FPN1 to the M. tuberculosis phagosome suggests that it is involved in regulating iron availability to the mycobacteria in this locale.
机译：包括结核分枝杆菌在内的细胞内病原体会从宿主体内获取铁以维持生存。 Ferroportin 1（FPN1; SLC40A1）是哺乳动物细胞的唯一铁输出物，在十二指肠和巨噬细胞中表达。在本研究中，我们显示小鼠巨噬细胞RAW264.7中的FPN1 mRNA水平是通过用活的或经伽马射线照射的结核分枝杆菌和IFN-γ协同诱导的。鸟分枝杆菌和IFN-γ在RAW264.7细胞和小鼠肺泡巨噬细胞系AMJ2-C8中也诱导了FPN1 mRNA的水平。用结核分枝杆菌和IFN-γ治疗小鼠常驻腹膜巨噬细胞导致FPN1 mRNA表达增加六倍。相比之下，结核分枝杆菌和IFN-γ抑制了骨髓来源的巨噬细胞和肺巨噬细胞中FPN1 mRNA表达水平较高的FPN1 mRNA表达。使用共聚焦显微镜，在RAW264.7巨噬细胞中感染后，FPN1蛋白迅速定位于结核分枝杆菌吞噬体。在表达野生型天然抗性相关巨噬细胞蛋白1（Nramp1（Gly169））的RAW264.7细胞中，FPN1和N​​ramp1在感染前在晚期内体/溶酶体中部分共定位。感染2小时后，结核分枝杆菌吞噬体中存在Nramp1和FPN1。我们的研究为病原性分枝杆菌和IFN-γ依赖于巨噬细胞类型提供了FPN1转录调控的证据。 FPN1向结核分枝杆菌吞噬体的运输表明，它参与调节该区域分枝杆菌的铁利用率。

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