Bano Nazneen, Romano Julia D, Jayabalasingham Bamini, Coppens Isabelle
Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, The Malaria Research Institute, 615 N. Wolfe Street, Baltimore, MD 21205, USA.
Int J Parasitol. 2007 Oct;37(12):1329-41. doi: 10.1016/j.ijpara.2007.04.005. Epub 2007 Apr 25.
The Plasmodium liver forms are bridgehead stages between the mosquito sporozoite stages and mammalian blood stages that instigate the malaria disease. In hepatocytes, Plasmodium achieves one of the fastest growth rates among eukaryotic cells. However, nothing is known about host hepatic cell interactions, e.g. nutrient scavenging and/or subversion of cellular functions necessary for Plasmodium development and replication. Plasmodium usually invades hepatocytes by establishing a parasitophorous vacuole wherein it undergoes multiple nuclear division cycles. We show that Plasmodium preferentially develops in the host juxtanuclear region. By comparison with the parasitophorous vacuole of other apicomplexan parasites which associate with diverse host organelles, the Plasmodium parasitophorous vacuole only forms an association with the host endoplasmic reticulum. Intrahepatic Plasmodium actively modifies the permeability of its vacuole to allow the transfer of a large variety of molecules from the host cytosol to the vacuolar space through open channels. In contrast with malaria blood stages, the pores within the parasitophorous vacuole membrane of the liver stage display a smaller size as they restrict the passage of solutes to less than 855Da. These pores are stably maintained during parasite karyokinesis until complete cellularisation. Host-derived cholesterol accumulated at the parasitophorous vacuole membrane may modulate the channel activity. These observations define the parasitophorous vacuole of the Plasmodium liver stage as a dynamic and highly permeable compartment that can ensure the sustained supply of host molecules to support parasite growth in the nutrient-rich environment of liver cells.
疟原虫肝期是蚊子子孢子阶段和引发疟疾的哺乳动物血液阶段之间的衔接阶段。在肝细胞中，疟原虫实现了真核细胞中最快的生长速度之一。然而，对于宿主肝细胞的相互作用，例如疟原虫发育和复制所需的营养物质清除和/或细胞功能的颠覆，我们却一无所知。疟原虫通常通过建立一个寄生泡来侵入肝细胞，在这个寄生泡中它会经历多个核分裂周期。我们发现疟原虫优先在宿主近核区域发育。与其他与多种宿主细胞器相关联的顶复门寄生虫的寄生泡相比，疟原虫的寄生泡仅与宿主内质网形成关联。肝内疟原虫会主动改变其泡的通透性，以允许各种各样的分子通过开放通道从宿主细胞质转移到泡腔内。与疟疾血液阶段不同，肝期寄生泡膜内的孔尺寸较小，因为它们将溶质的通过限制在小于855Da。这些孔在寄生虫核分裂期间稳定维持，直到完全细胞化。宿主来源的胆固醇在寄生泡膜处积累可能会调节通道活性。这些观察结果将疟原虫肝期的寄生泡定义为一个动态且高度通透的区室，它能够确保持续供应宿主分子，以支持疟原虫在富含营养的肝细胞环境中生长。
