Parasite‐induced ER stress response in hepatocytes facilitates Plasmodium liver stage infection. (25th June 2015)

• Record Type: Journal Article
• Authors: Inácio, Patricia; Zuzarte‐Luís, Vanessa; Ruivo, Margarida TG; Falkard, Brie; Nagaraj, Nagarjuna; Rooijers, Koos; Mann, Matthias; Mair, Gunnar; Fidock, David A; Mota, Maria M
• Is Part Of: EMBO reports. Volume 16:Number 8(2015:Aug.)
• Page Start: 955
• Page End: 964
• Publication Date: 2015-06-25
• Subjects: Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.201439979
• Languages: English
• ISSNs: 1469-221X

Abstract

<abstract abstract-type="main" id="embr201439979-abs-0001"> <title>Abstract</title> <p>Upon infection of a mammalian host, <italic>Plasmodium</italic> parasites first replicate inside hepatocytes, generating thousands of new parasites. Although <italic>Plasmodium</italic> 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 <italic>Plasmodium berghei</italic> infection. The expression of XBP1s—the active form of the UPR mediator XBP1—and the liver‐specific UPR mediator CREBH is induced by <italic>P. berghei</italic> infection <italic>in vivo</italic>. Furthermore, this UPR induction increases parasite liver burden. Altogether, our data suggest that ER stress is a central feature of <italic>P. berghei</italic> intra‐hepatic development, contributing to the success of infection.</p> </abstract>