Studies on the Mechanisms of Stage specific Host Infection in Malarial Parasite

疟原虫阶段特异性宿主感染机制研究

基本信息

批准号：
17209014
负责人：
CHINZEI Yasuo
金额：
$ 30.37万
依托单位：
Suzuka University of Medical Science (2007)Mie University (2005-2006)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

项目摘要

The summary of this project performed in this three years is shown below. Malarial parasite is transmitted by Anopheline mosquito. Parasite ookinete and sporozoite invade and pass through the mosquito mig-gut epithlium cell and the salivary gland cell, and formed in the mosquito mid gut lumen by sexual fusion passes through the mid-gut epithelium and forms a oocyst on the gut wall. Salivary gland sporozoite injected into the host by mosquito bite has to pass through the skin barriers and River sinusoidal cell layer to reach and infect the hepatocyte. We planned to investigate the molecular mechanisms of the parasite invasion into those barrier cells. For this purpose, we used a rodent malarial parasite Plasmodium berghei as a model animal, and analyzed the EST (expressed sequence tags) of ookinete and sporozoite. We selected gene by a criteria from the EST and generated parasite disrupted the gene. A function of the gene was studied by the analyses of the phenotype of the gene disrupted parasite. As results, we identified MAOP and MAEBL for essential molecules for invasion to mig-gut epithelial cell and the salivary gland cell. And we also identified two molecules, SPECT1 and 2 for essential molecules to invade into the Kupffer cell in the sinusoidal cell layer of the liver. We identified OSM-1, a molecule essential for translocation through the mid-gut cell and Kupffer cell from the ookinete and sporozoite. We demonstrated the common mechanisms of the cell passage of ookinete and sporozoite through the barrier cell layer, the mosquito mid-gut cell and the sinusoidal cell layer. We also demonstrated first for the sporozoite to pass through the Kupffer cell in the sinusoidal layer to reach the hepatocyte to infect from the sinusoid.

该项目近三年来的实施情况总结如下。疟疾寄生虫通过按蚊传播。寄生虫动动子和子孢子侵入并穿过蚊子中肠上皮细胞和唾液腺细胞，在蚊子中肠腔内通过有性融合形成，穿过中肠上皮，在肠壁上形成卵囊。蚊虫叮咬注入宿主的唾液腺子孢子必须穿过皮肤屏障和河窦细胞层到达并感染肝细胞。我们计划研究寄生虫侵入这些屏障细胞的分子机制。为此，我们使用啮齿类疟疾寄生虫伯氏疟原虫作为模型动物，并分析了动动体和子孢子的EST（表达序列标签）。我们根据 EST 的标准选择基因，并生成破坏该基因的寄生虫。通过分析基因被破坏的寄生虫的表型来研究该基因的功能。结果，我们确定了 MAOP 和 MAEBL 是侵袭小肠上皮细胞和唾液腺细胞的必需分子。我们还鉴定了两种分子：SPECT1 和 2，它们是侵入肝窦细胞层库普弗细胞的必需分子。我们鉴定出了 OSM-1，一种从动动子和子孢子中穿过中肠细胞和库普弗细胞易位所必需的分子。我们展示了动动子和子孢子穿过屏障细胞层、蚊子中肠细胞和正弦细胞层的细胞通道的共同机制。我们还首次证明了子孢子穿过肝窦层的库普弗细胞到达肝细胞并从肝窦感染。