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首页> 外文期刊>Cell discovery. >Hemojuvelin regulates the innate immune response to peritoneal bacterial infection in mice
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Hemojuvelin regulates the innate immune response to peritoneal bacterial infection in mice

机译：血茱vel素调节小鼠对腹膜细菌感染的天然免疫反应

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Hereditary hemochromatosis and iron imbalance are associated with susceptibility to bacterial infection; however, the underlying mechanisms are poorly understood. Here, we performed in vivo bacterial infection screening using several mouse models of hemochromatosis, including Hfe ( Hfe ?/? ), hemojuvelin ( Hjv ?/? ), and macrophage-specific ferroportin-1 ( Fpn1 fl/fl ; LysM-Cre + ) knockout mice. We found that Hjv ?/? mice, but not Hfe ?/? or Fpn1 fl/fl ; LysM-Cre + mice, are highly susceptible to peritoneal infection by both Gram-negative and Gram-positive bacteria. Interestingly, phagocytic cells in the peritoneum of Hjv ?/? mice have reduced bacterial clearance, IFN-γ secretion, and nitric oxide production; in contrast, both cell migration and phagocytosis are normal. Expressing Hjv in RAW264.7 cells increased the level of phosphorylated Stat1 and nitric oxide production. Moreover, macrophage-specific Hjv knockout mice are susceptible to bacterial infection. Finally, we found that Hjv facilitates the secretion of IFN-γ via the IL-12/Jak2/Stat4 signaling pathway. Together, these findings reveal a novel protective role of Hjv in the early stages of antimicrobial defense.
机译：遗传性血色素沉着症和铁不平衡与细菌感染的易感性有关。但是，对潜在的机制了解甚少。在这里，我们使用几种血色素沉着症小鼠模型进行了体内细菌感染筛选，包括Hfe（Hfe ？/？），hemojuvelin（Hjv ？/？）和巨噬细胞-特异性铁转运蛋白-1（Fpn1 fl / fl ; LysM-Cre + ）基因敲除小鼠。我们发现Hjv ？/？小鼠，但不是Hfe ？/？ 或Fpn1 fl / fl ; LysM-Cre + 小鼠对革兰氏阴性菌和革兰氏阳性菌都非常容易受到腹膜感染。有趣的是，Hjv ？/？小鼠腹膜中的吞噬细胞具有降低的细菌清除率，IFN-γ分泌和一氧化氮的产生。相反，细胞迁移和吞噬作用均正常。在RAW264.7细胞中表达Hjv增加了磷酸化Stat1和一氧化氮的产生。此外，巨噬细胞特异性Hv敲除小鼠易受细菌感染。最后，我们发现Hjv通过IL-12 / Jak2 / Stat4信号通路促进IFN-γ的分泌。总之，这些发现揭示了Hjv在抗菌防御的早期阶段具有新型的保护作用。

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