Carrolo Margarida, Giordano Silvia, Cabrita-Santos Laura, Corso Simona, Vigário Ana M, Silva Susana, Leirião Patricia, Carapau Daniel, Armas-Portela Rosario, Comoglio Paolo M, Rodriguez Ana, Mota Maria M
Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, 2780-156 Oeiras, Portugal.
Nat Med. 2003 Nov;9(11):1363-9. doi: 10.1038/nm947. Epub 2003 Oct 12.
Plasmodium, the causative agent of malaria, must first infect hepatocytes to initiate a mammalian infection. Sporozoites migrate through several hepatocytes, by breaching their plasma membranes, before infection is finally established in one of them. Here we show that wounding of hepatocytes by sporozoite migration induces the secretion of hepatocyte growth factor (HGF), which renders hepatocytes susceptible to infection. Infection depends on activation of the HGF receptor, MET, by secreted HGF. The malaria parasite exploits MET not as a primary binding site, but as a mediator of signals that make the host cell susceptible to infection. HGF/MET signaling induces rearrangements of the host-cell actin cytoskeleton that are required for the early development of the parasites within hepatocytes. Our findings identify HGF and MET as potential targets for new approaches to malaria prevention.
疟原虫是疟疾的病原体，它必须首先感染肝细胞才能引发哺乳动物感染。子孢子在最终在其中一个肝细胞中建立感染之前，会通过破坏肝细胞的质膜穿过多个肝细胞。我们在此表明，子孢子迁移对肝细胞造成的损伤会诱导肝细胞生长因子（HGF）的分泌，这使得肝细胞易于被感染。感染取决于分泌的HGF对HGF受体MET的激活。疟原虫利用MET并非作为主要结合位点，而是作为使宿主细胞易于被感染的信号介质。HGF/MET信号传导诱导宿主细胞肌动蛋白细胞骨架重排，这是疟原虫在肝细胞内早期发育所必需的。我们的研究结果确定HGF和MET是疟疾预防新方法的潜在靶点。
