title: Parasite-induced ER stress response in hepatocytes facilitates Plasmodium liver stage infection.
abstract: 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.
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Patricia
authors.initials: P
authors.lastname: Inácio
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Zuzarte-Luís
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Margarida T G
authors.initials: MT
authors.lastname: Ruivo
authors.affiliation: Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Brie
authors.initials: B
authors.lastname: Falkard
authors.affiliation: Department of Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, Martinsried, Germany.
authors.forename: Nagarjuna
authors.initials: N
authors.lastname: Nagaraj
authors.affiliation: Division of Gene Regulation, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Koos
authors.initials: K
authors.lastname: Rooijers
authors.affiliation: Department of Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, Martinsried, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
authors.affiliation: Department of Parasitology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Mair
authors.affiliation: Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY, USA Division of Infectious Diseases, Department of Medicine, Columbia University Medical Center, New York, NY, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Fidock
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal mmota@medicina.ulisboa.pt.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Mota
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics; D059865:Endoplasmic Reticulum Stress; D020869:Gene Expression Profiling; D022781:Hepatocytes / Q000469:parasitology* / Q000502:physiology / Q000648:ultrastructure; D006790:Host-Parasite Interactions; D008018:Life Cycle Stages; D008288:Malaria / Q000469:parasitology* / Q000503:physiopathology; D008297:Male; D008810:Mice, Inbred C57BL; D059208:Parasite Load; D010962:Plasmodium berghei / Q000254:growth & development* / Q000472:pathogenicity; D040901:Proteomics; D000071701:Regulatory Factor X Transcription Factors; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D056811:Unfolded Protein Response; D000071717:X-Box Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse
keywords: CREBH; Plasmodium; UPR; XBP1; liver