MALARIA LIVER INFECTION & INITATION OF IMMUNE RESPONSE

描述：疟原虫子孢子如何侵入肝细胞，并在 他们，在很大程度上仍然不为人所知。我们的初步研究表明 子孢子可以通过破坏宿主细胞而迅速进入和离开宿主细胞。 质膜。在非生产性进出的几个周期之后，子孢子 侵入宿主细胞，发育为红外期。我们建议 子孢子通过几个细胞是必需的成熟 在生命周期中的一步，它发生在寄生虫从 皮肤进入肝脏的部位。这一假设将得到检验。 使用细胞和分子生物学方法，包括体外和体内 肝细胞感染模型。 我们的初步研究表明，疟原虫的子孢子确保了他们的 通过抑制细胞凋亡而完全发育为红外期 肝细胞。相反，在感染前照射子孢子 导致肝细胞凋亡。我们建议确定遗传途径 参与抑制肝细胞凋亡，并鉴定疟原虫 通过检测宿主中的基因表达，参与这一过程的基因 和病原体在有无辐射的情况下。保护性免疫 对疟疾的反应是通过用辐照的子孢子免疫来诱导的。我们 提示感染猪瘟病毒的肝细胞产生的凋亡小体 辐照的子孢子介导保护性抗疟疾的启动 免疫反应。将使用免疫学和细胞生物学方法来 在体外和体内进一步检验这一假说。

DESCRIPTION: How Plasmodium sporozoites invade hepatocytes, and develop within them, remains largely unknown. Our Preliminary Studies indicate that sporozoites can rapidly enter and leave host cells by disrupting the host cell plasma membrane. After few cycles of non-productive entry and exit, sporozoites invade host cells, and develop into the exo-erythrocytic stages. We propose that the passage of sporozoites through several cells is a required maturation step in the life cycle, and that it occurs during the parasite's journey from the site of entry in the skin to the liver. This hypothesis will be tested using cell and molecular biology approaches involving in vitro and in vivo models for hepatocyte infection. Our Preliminary Studies suggest that Plasmodium sporozoites ensure their complete development into the exo-erythrocytic stages by inhibiting apoptosis of hepatocytes. In contrast, irradiation of sporozoites prior to infection results in hepatocyte apoptosis. We propose to determine the genetic pathways involved in apoptosis inhibition of hepatocytes, and to identify the Plasmodium genes that contribute to this process, by examining gene expression in the host and pathogen in the presence and absence of irradiation. A protective immune response to malaria is induced by immunization with irradiated sporozoites. We propose that the apoptotic bodies derived from hepatocytes infected with irradiated sporozoites mediate the initiation of a protective anti-malaria immune response. Immunological and cell biological approaches will be used to further examine this hypothesis in vitro and in vivo.