Influence of Iron on Murine Malaria

铁对小鼠疟疾的影响

基本信息

批准号：
8124884
负责人：
DAVID Joseph SULLIVAN
金额：
$ 19.39万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2013-07-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Iron supplementation in iron replete, but not iron deficient children has been shown to increase malaria associated morbidity. Iron chelators, while cytostatic for bacterial and mammalian cells, actually kill malaria parasites, despite the availability of millimolar heme iron in the infected erythrocyte. Iron repletion has not been fully evaluated in murine malaria models. The broad long term objective is to rapidly evaluate the type of iron supplementation and timing of malaria infection during iron repletion on malaria morbidity in mice with implications for human nutritional iron supplementation. We hypothesize that parasite bioavailable iron excess influences the hepatic stage significantly more than erythrocytic stage of malaria. The type of iron supplementation or timing of malaria infection during iron replenishment will alter malaria outcome possibly dependent on an iron effect on immune function rather than the erythrocyte iron level. The specific aims are 1) to compare the type of iron supplementation and timing of malaria infection in iron deficient and iron replete mice on both hepatic and erythrocytic stage malaria; 2) to evaluate the influence of iron supplementation and timing of malaria infection in genotypic iron defective mice for hepcidin or also erythroid, not hepatic, iron uptake and 3) to correlate malaria outcomes with hematologic biomarkers like hepcidin, erythrocyte ferritin and murine zinc protoporphyrin IX or immunologic biomarkers like interferon-gamma. The techniques to be utilized include mouse malaria testing, iron profiling and biomarker assays. These studies will be able to distinguish erythrocyte iron status from host immune response in malaria outcome with iron supplementation. The significant impact is to rapidly evaluate the method and type of iron therapy on malaria morbidity in mice with implications for human nutritional iron supplementation for children at risk of malaria. PUBLIC HEALTH RELEVANCE: This research will investigate the influence of iron supplementation in a mouse malaria model. The type of iron supplementation and timing of malaria infection during iron repletion on liver stage and blood cell stage malaria outcomes will be evaluated in iron deficient, iron replete and iron defective mice. Hematologic and immunologic biomarkers associated with outcome will be correlated

描述（由申请人提供）：铁的补充铁，但尚未证明不足的儿童可以增加疟疾相关的发病率。铁螯合剂虽然细菌和哺乳动物细胞的细胞抑制剂实际上杀死了疟疾寄生虫，尽管感染的红细胞中有毫米性的血红素铁。在鼠类疟疾模型中尚未对铁的补充进行全面评估。广义的长期目标是快速评估铁充血期间对小鼠疟疾发病率的疟疾感染的补充类型和时间，对人类营养铁的补充有影响。我们假设寄生虫可生物利用铁的过量影响肝阶段明显比疟疾的红细胞阶段更大。铁补充过程中补充铁的类型或疟疾感染的时间可能会改变疟疾结果可能取决于铁对免疫功能的影响而不是红细胞铁水平。具体目的是1）比较在肝和红细胞性疟疾上的铁不足和铁毛小鼠中疟疾感染的补充类型和疟疾感染的时间； 2）评估疟疾感染对基因型铁缺陷小鼠的补充和时间的影响肝素或红系，而不是肝，铁吸收和3）将疟疾结局与肝素生物标记物相关联，例如肝素生物标志物，例如肝素，红细胞铁蛋白和鼠锌原生质 - 原生石IX或类似于Interferon-Gamma的免疫生物标志物。要使用的技术包括小鼠疟疾测试，铁谱和生物标志物测定法。这些研究将能够区分红细胞铁的状态与宿主免疫反应在疟疾结局中补充铁。重要的影响是快速评估铁治疗对小鼠疟疾发病率的方法和类型，对疟疾风险的儿童补充人类营养铁的影响。公共卫生相关性：这项研究将研究补充铁在小鼠疟疾模型中的影响。在肝脏阶段和血细胞阶段疟疾结局期间，将在铁不足，铁饱和和铁缺陷的小鼠中评估铁补充期间疟疾感染的铁的类型和疟疾感染的时间。与结果相关的血液学和免疫生物标志物将是相关的