Hemojuvelin regulates the innate immune response to peritoneal bacterial infection in mice

Qian Wu, Yuanyuan Shen, Yunlong Tao, Jiayu Wei, Hao Wang, Peng An, Zhuzhen Zhang, Hong Gao, Tianhua Zhou, Fudi Wang, Junxia Min

Research output: Contribution to journalArticlepeer-review

Abstract

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 (Fpn1fl/fl; LysM-Cre+) knockout mice. We found that Hjv− / − mice, but not Hfe−/− or Fpn1fl/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.

Original languageEnglish (US)
Article number17028
JournalCell Discovery
Volume3
Issue number1
DOIs
StatePublished - 2017
Externally publishedYes

Keywords

  • Hemochromatosis
  • Hemojuvelin
  • Innate immune
  • Iron
  • Macrophage

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Fingerprint

Dive into the research topics of 'Hemojuvelin regulates the innate immune response to peritoneal bacterial infection in mice'. Together they form a unique fingerprint.

Cite this