The Protozoan Parasite Toxoplasma gondii Selectively Reprograms the Host Cell Translatome
| Autor: | Julie Lorent, Maritza Jaramillo, Laia Masvidal, Tommy Alain, Ola Larsson, Visnu Chaparro, Bruno D. Fonseca, Tyson E. Graber, Léon C van Kempen, Maria Aguirre, Louis-Philippe Leroux |
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| Přispěvatelé: | Institut Armand Frappier (INRS-IAF), Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS), Karolinska Institutet [Stockholm], University of Ottawa [Ottawa], Jewish General Hospital, McGill University = Université McGill [Montréal, Canada], University Medical Center Groningen [Groningen] (UMCG), This work was supported by a Basil O'Connor starter scholar research award (5-FY14-78) and a research grant (6-FY16-151) from The March of Dimes Foundation to M.J. The Centre for Host-Parasite Interactions is supported by a Subvention de Regroupement Stratégique from the Fonds de Recherche du Québec en Nature et Technologies (FRQ-NT). M.J. is a recipient of a Bourse de Chercheur-Boursier Junior 1 from the Fonds de Recherche du Québec en Santé (FRQ-S) and a Subvention d'Établissement de Jeune Chercheur from the FRQ-S. V.C. is supported by a Ph.D. scholarship from the Fondation Universitaire Armand Frappier. Research in the laboratory of O.L. is supported by grants from the Swedish Research Council and the Wallenberg Academy Fellows program., We are grateful to Nahum Sonenberg for providing bone marrow from C57BL/6 s6k1−/− s6k2−/− mice (McGill University, Montreal, QC, Canada). We thank Medhi Jafarnejad (McGill University) for technical advice. We are thankful to Annie Sylvestre and Annik Lafrance for invaluable technical assistance. We acknowledge support from the Science for Life Laboratory, the National Genomics Infrastructure (NGI), and Uppmax for providing assistance in massive parallel sequencing and computational infrastructure. |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
MESH: Signal Transduction
0301 basic medicine DIFFERENTIAL TRANSLATION Protozoan Proteins MESH: Toxoplasma/pathogenicity RNA 5' Terminal Oligopyrimidine Sequence MESH: Mice Knockout Mice Poly(A)-binding protein Protein biosynthesis host-pathogen interactions MESH: Animals Cells Cultured Mice Knockout biology IMMUNE-RESPONSES TOR Serine-Threonine Kinases translational control Translation (biology) Cell biology macrophages Infectious Diseases MESSENGER-RNA TRANSLATION mTOR PROTEIN-SYNTHESIS MESH: Host-Parasite Interactions [SDV.IMM]Life Sciences [q-bio]/Immunology Toxoplasma Signal Transduction MESH: Cells Cultured Translational efficiency Immunology ENDOPLASMIC-RETICULUM MESH: RNA 5' Terminal Oligopyrimidine Sequence Toxoplasma gondii Microbiology DENDRITIC CELLS Host-Parasite Interactions POLY(A)-BINDING PROTEINS Mitochondrial Proteins 03 medical and health sciences MESH: Protein Biosynthesis/genetics MESH: Mice Inbred C57BL PARASITOPHOROUS VACUOLE MEMBRANE parasitic diseases Animals MESH: Mice Mechanistic target of rapamycin Cellular Microbiology: Pathogen-Host Cell Molecular Interactions 030102 biochemistry & molecular biology Intracellular parasite biology.organism_classification MESH: Protozoan Proteins/immunology Cytoplasm organization Mice Inbred C57BL MESH: Mitochondrial Proteins/genetics MAMMALIAN-TARGET 030104 developmental biology Protein Biosynthesis MESH: TOR Serine-Threonine Kinases/genetics biology.protein INNATE IMMUNITY MESH: Macrophages/parasitology Parasitology |
| Zdroj: | Infection and Immunity Infection and Immunity, American Society for Microbiology, 2018, 86 (9), pp.e00244-18. ⟨10.1128/IAI.00244-18⟩ Infection and Immunity, 86(9):ARTN e00244-18. AMER SOC MICROBIOLOGY |
| ISSN: | 0019-9567 1098-5522 |
| DOI: | 10.1128/iai.00244-18 |
| Popis: | International audience; The intracellular parasite Toxoplasma gondii promotes infection by targeting multiple host cell processes; however, whether it modulates mRNA translation is currently unknown. Here, we show that infection of primary murine macrophages with type I or II T. gondii strains causes a profound perturbation of the host cell translatome. Notably, translation of transcripts encoding proteins involved in metabolic activity and components of the translation machinery was activated upon infection. In contrast, the translational efficiency of mRNAs related to immune cell activation and cytoskeleton/cytoplasm organization was largely suppressed. Mechanistically, T. gondii bolstered mechanistic target of rapamycin (mTOR) signaling to selectively activate the translation of mTOR-sensitive mRNAs, including those with a 5'-terminal oligopyrimidine (5' TOP) motif and those encoding mitochondrion-related proteins. Consistent with parasite modulation of host mTOR-sensitive translation to promote infection, inhibition of mTOR activity suppressed T. gondii replication. Thus, selective reprogramming of host mRNA translation represents an important subversion strategy during T. gondii infection. |
| Databáze: | OpenAIRE |
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