Two proteins with 6-cys motifs are required for malarial parasites to commit to infection of the hepatocyte
Two proteins with 6-cys motifs are required for malarial parasites to commit to infection of the hepatocyte
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DOI：
10.1111/j.1365-2958.2005.04801.x
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发表时间：
2005-12-01
影响因子：
3.6
通讯作者：
Yuda, M
中科院分区：
文献类型：
--
作者：
Ishino, T;Chinzei, Y;Yuda, M
许多细胞内病原体具有适合其增殖的宿主细胞，并使用特定的宿主-寄生虫相互作用选择性地侵入它们。疟疾子孢子是一种侵入肝脏的形式，它能有效地靶向肝细胞并在其中增殖。然而，到目前为止，介导肝细胞特异性感染的子孢子分子仍然未知。在这里，我们报告，两个蛋白质，Pbs 36 p和Pbs 36，属于疟原虫6-cys结构域蛋白质家族，执行这一功能。我们发现，这些分子是专门生产的肝脏感染的子孢子。各个基因的靶向破坏几乎消除了哺乳动物宿主中的子孢子感染性。侵袭试验表明，突变体寄生虫不能承诺感染，即使当他们遇到肝细胞，导致肝细胞的连续遍历。这些结果表明，这些蛋白质是必要的子孢子识别肝细胞和承诺的感染。这一发现可能导致新的抗疟疾策略，防止子孢子感染的肝细胞。
Many intracellular pathogens have host cells suitable for their proliferation, and selectively invade them using specific host-parasite interactions. Malarial sporozoites, the liver-invasive forms, are effectively targeted to hepatocytes and proliferate in them. So far, however, sporozoite molecules that mediate the specific infection of hepatocytes remain unknown. Here we report that two proteins, Pbs36p and Pbs36, belonging to the plasmodium 6-cys domain protein family, carry out this function. We found that these molecules are specifically produced in liver-infective sporozoites. Target disruption of the respective genes nearly abolished sporozoite infectivity in the mammalian host. Invasion assays revealed that the mutant parasites could not commit to infection, even when they encounter with hepatocytes, resulting in continuous traversal of hepatocytes. These results suggest that these proteins are necessary for sporozoites to recognize hepatocytes and commit to infection. This finding might lead to novel anti-malarial strategies that prevent sporozoite infection of the hepatocyte.