Hepcidin-induced hypoferremia is a critical host defense mechanism against the siderophilic bacterium Vibrio vulnificus.
Hepcidin-induced hypoferremia is a critical host defense mechanism against the siderophilic bacterium Vibrio vulnificus.
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DOI：
10.1016/j.chom.2014.12.001
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发表时间：
2015-01-14
影响因子：
30.3
通讯作者：
Bulut Y
中科院分区：
文献类型：
--
作者：
Arezes J;Jung G;Gabayan V;Valore E;Ruchala P;Gulig PA;Ganz T;Nemeth E;Bulut Y
遗传性血色素沉着症是一种由铁调节激素铁调素缺乏引起的铁超载疾病，与嗜铁细菌的致命感染有关。为了阐明这种易感性的机制，我们用嗜铁细菌创伤弧菌感染野生型和铁调素缺乏的小鼠，发现铁调素缺乏导致感染小鼠的菌血症增加和存活率降低，这可以通过膳食铁耗竭部分改善。此外，及时向铁调素缺陷型小鼠施用铁调素激动剂诱导低铁血症，其降低细菌负荷并将这些小鼠从死亡中拯救出来，而不管初始铁水平如何。创伤弧菌体外生长的研究表明，铁调素缺乏小鼠的高铁血清支持非常快速的细菌生长，并且这在低铁血清中被抑制。我们的研究结果表明，铁调素介导的低铁血症是一种宿主防御机制，对嗜铁病原体，并建议铁调素激动剂可能会改善感染的遗传性血色素沉着症或地中海贫血患者的结果。
Hereditary hemochromatosis, an iron overload disease caused by a deficiency in the iron-regulatory hormone hepcidin, is associated with lethal infections by siderophilic bacteria. To elucidate the mechanisms of this susceptibility, we infected wild-type and hepcidin-deficient mice with the siderophilic bacterium Vibrio vulnificus, and found that hepcidin deficiency results in increased bacteremia and decreased survival of infected mice, which can be partially ameliorated by dietary iron depletion. Additionally, timely administration of hepcidin agonists to hepcidin-deficient mice induces hypoferremia that decreases bacterial loads and rescues these mice from death, regardless of initial iron levels. Studies of Vibrio vulnificus growth ex vivo show that high iron sera from hepcidin-deficient mice support extraordinarily rapid bacterial growth, and that this is inhibited in hypoferremic sera. Our findings demonstrate that hepcidin-mediated hypoferremia is a host defense mechanism against siderophilic pathogens and suggest that hepcidin agonists may improve infection outcomes in patients with hereditary hemochromatosis or thalassemia.
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影响因子：
29
作者：
Donovan, A;Lima, CA;Andrews, NC
通讯作者：
Andrews, NC
影响因子：
20.3
作者：
Falzacappa, Maria Vittoria Verga;Spasic, Maja Vujic;Muckenthaler, Martina U.
通讯作者：
Muckenthaler, Martina U.
影响因子：
6.4
作者：
Kim, Choon-Mee;Park, Ra-Young;Shin, Sung-Heui
通讯作者：
Shin, Sung-Heui
影响因子：
20.3
作者：
Esposito, BP;Breuer, W;Cabantchik, ZI
通讯作者：
Cabantchik, ZI
影响因子：
2.8
作者：
Bisharat, Naiel;Bronstein, Michal;Koton, Yael
通讯作者：
Koton, Yael