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


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-? 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-? 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.

SUBMITTER: Wu Q 

PROVIDER: S-EPMC5556331 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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

Wu Qian Q   Shen Yuanyuan Y   Tao Yunlong Y   Wei Jiayu J   Wang Hao H   An Peng P   Zhang Zhuzhen Z   Gao Hong H   Zhou Tianhua T   Wang Fudi F   Min Junxia J  

Cell discovery 20170815


Hereditary hemochromatosis and iron imbalance are associated with susceptibility to bacterial infection; however, the underlying mechanisms are poorly understood. Here, we performed <i>in vivo</i> bacterial infection screening using several mouse models of hemochromatosis, including <i>Hfe</i> (<i>Hfe</i><sup><i>-/-</i></sup> ), <i>hemojuvelin</i> (<i>Hjv</i><sup><i>-/-</i></sup> ), and macrophage-specific <i>ferroportin-1</i> (<i>Fpn1</i><sup><i>fl/fl</i></sup> ;<i>LysM-Cre</i><sup><i>+</i></su  ...[more]

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