期刊
CELL DISCOVERY
卷 3, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/celldisc.2017.28
关键词
hemochromatosis; hemojuvelin; iron; innate immune; macrophage
类别
资金
- National Natural Science Foundation of China [31530034, 31330036, 31225013, 31570791, 91542205]
- Zhejiang Provincial Natural Science Foundation of China [LZ15H160002]
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-gamma 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-gamma 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.
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