首页> 外文学位 >Development of efficient tools for analysis of the host-parasite interaction during the liver stages of malaria infection.
【24h】

Development of efficient tools for analysis of the host-parasite interaction during the liver stages of malaria infection.

机译:开发用于分析疟疾感染肝脏阶段宿主-寄生虫相互作用的有效工具。

获取原文
获取原文并翻译 | 示例

摘要

The morbidity and mortality due to malaria is rising as a result of the emergence and spread of drug resistant parasites and the lack of an effective vaccine. Development of novel intervention strategies is hindered by the lack of efficient tools available to study liver stage parasites in vivo . Development of Plasmodium parasites in the liver is the first and obligatory step in its life cycle in the vertebrate host. Although a clinically silent infection, development of parasites in the liver is an immunologically active stage leading to protective immunity. It is thus imperative that we develop novel tools to study the biology of Plasmodium liver stages.;First, to study sporozoites-hepatocytes molecular interactions, we adapted transfection of mouse hepatocytes by hydrodynamic tail vein injection to deliver naked DNA to hepatocytes in vivo. Transfection by hydrodynamic injection can lead to creation of disease models and non-heritable transgenic research animals within a short time. With further optimization of experimental conditions, transfection by hydrodynamic injection is a promising invaluable tool to study molecular interactions between sporozoites and hepatocytes in vivo.;Second, for thorough screening of factors that affect liver stage parasite growth, we adapted bioluminescent imaging (BLI) of P. yoelii YM expressing firefly luciferase (PyLuc). BLI is a non-invasive and rapid technique that allows for real-time monitoring of infection in the same animal. Using BLI, for the first time, in vivo liver stage parasites were imaged after infecting mice with PyLuc sporozoites and effects of drugs and immunization on this stage were quantified. BLI allows for efficient analysis of effects of chemotherapeutic or vaccine candidates on liver stages.;Successful efforts to combat the devastation of malaria require understanding of how the parasite and host interact during infection. It is not entirely clear how the Plasmodium parasites establish infection, and how the host immune system responds to parasites. We have adapted transfection by hydrodynamic injection and bioluminescent imaging as important tools to study parasite biology in vivo. These important tools will help to better understand parasite biology thus leading to generation of effective intervention strategies to reduce the morbidity and mortality caused by malaria.
机译:由于抗药性寄生虫的出现和扩散以及缺乏有效疫苗的结果,疟疾的发病率和死亡率正在上升。缺乏有效的工具来研究体内肝期寄生虫阻碍了新干预策略的发展。在脊椎动物宿主中,肝脏中疟原虫的发展是其生命周期中的第一步,也是必不可少的步骤。尽管是临床上无症状的感染,但肝脏中寄生虫的形成是导致保护性免疫的免疫活性阶段。因此,我们必须开发新的工具来研究疟原虫肝阶段的生物学特性。首先,为了研究子孢子-肝细胞的分子相互作用,我们通过流体动力尾静脉注射适应了小鼠肝细胞的转染,以将裸露的DNA体内递送至肝细胞。通过流体动力注射进行转染可导致在短时间内创建疾病模型和非遗传性转基因研究动物。随着实验条件的进一步优化,流体动力注射转染是研究体内子孢子与肝细胞之间分子相互作用的有前途的宝贵工具。第二,为了彻底筛选影响肝阶段寄生虫生长的因素,我们采用了生物发光成像(BLI)。表达萤火虫荧光素酶(PyLuc)的约氏疟原虫YM。 BLI是一种非侵入性的快速技术,可实时监控同一只动物的感染情况。首次使用BLI,在用PyLuc子孢子感染小鼠后,对体内肝脏阶段的寄生虫进行了成像,并量化了该阶段的药物和免疫效果。 BLI可以有效分析化学疗法或候选疫苗对肝脏阶段的影响。要成功地抗击疟疾,需要了解寄生虫和宿主在感染过程中如何相互作用。尚不清楚疟原虫寄生虫如何建立感染,以及宿主免疫系统如何对寄生虫作出反应。我们已经将通过流体动力注射和生物发光成像进行的转染调整为研究体内寄生虫生物学的重要工具。这些重要工具将有助于更好地了解寄生虫生物学,从而导致产生有效的干预策略,以减少由疟疾引起的发病率和死亡率。

著录项

  • 作者

    Mwakingwe, Agnes.;

  • 作者单位

    Yeshiva University.;

  • 授予单位 Yeshiva University.;
  • 学科 Biology Microbiology.;Health Sciences Immunology.;Biology Parasitology.;Health Sciences Epidemiology.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 286 p.
  • 总页数 286
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 微生物学;预防医学、卫生学;
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号