Parasite-induced ER stress response in hepatocytes facilitates Plasmodium liver stage infection
Parasite-induced ER stress response in hepatocytes facilitates Plasmodium liver stage infection
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DOI：
10.15252/embr.201439979
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发表时间：
2015-08-01
期刊：
影响因子：
7.7
通讯作者：
Mota, Maria M.
中科院分区：
文献类型：
--
作者：
Inacio, Patricia;Zuzarte-Luis, Vanessa;Mota, Maria M.
一旦感染哺乳动物宿主，疟原虫首先在肝细胞内复制，产生数千种新的寄生虫。虽然疟原虫在肝内的发育对宿主肝细胞来说是一个巨大的代谢挑战，但感染细胞如何响应和整合这种应激仍然知之甚少。在这里，我们提供蛋白质组和转录组分析，揭示内质网(ER)驻留的未折叠蛋白反应(UPR)在伯氏疟原虫感染后在宿主肝细胞中被激活。UPR介导物XBP1的活性形式XBP1s和肝脏特异性UPR介导物CREBH的表达是由伯氏假单胞菌感染体内诱导的。此外，这种UPR诱导增加了寄生虫的肝脏负担。总之，我们的数据表明，内质网应激是伯氏肺孢子虫肝内发育的一个中心特征，有助于感染的成功。
Upon infection of a mammalian host, Plasmodium parasites first replicate inside hepatocytes, generating thousands of new parasites. Although Plasmodium intra-hepatic development represents a substantial metabolic challenge to the host hepatocyte, how infected cells respond to and integrate this stress remains poorly understood. Here, we present proteomic and transcriptomic analyses, revealing that the endoplasmic reticulum (ER)-resident unfolded protein response (UPR) is activated in host hepatocytes upon Plasmodium berghei infection. The expression of XBP1s-the active form of the UPR mediator XBP1-and the liver-specific UPR mediator CREBH is induced by P. berghei infection in vivo. Furthermore, this UPR induction increases parasite liver burden. Altogether, our data suggest that ER stress is a central feature of P. berghei intra-hepatic development, contributing to the success of infection.