PMID- 29967092 OWN - NLM STAT- MEDLINE DCOM- 20190305 LR - 20211204 IS - 1098-5522 (Electronic) IS - 0019-9567 (Print) IS - 0019-9567 (Linking) VI - 86 IP - 9 DP - 2018 Sep TI - The Protozoan Parasite Toxoplasma gondii Selectively Reprograms the Host Cell Translatome. LID - 10.1128/IAI.00244-18 [doi] LID - e00244-18 AB - 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. CI - Copyright (c) 2018 American Society for Microbiology. FAU - Leroux, Louis-Philippe AU - Leroux LP AUID- ORCID: 0000-0002-9736-1827 AD - Institut National de la Recherche Scientifique-Institut Armand Frappier, Laval, Quebec, Canada. AD - Centre for Host-Parasite Interactions, Institut National de la Recherche Scientifique-Institut Armand Frappier, Laval, Quebec, Canada. FAU - Lorent, Julie AU - Lorent J AD - Department of Oncology-Pathology, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden. FAU - Graber, Tyson E AU - Graber TE AD - Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada. FAU - Chaparro, Visnu AU - Chaparro V AD - Institut National de la Recherche Scientifique-Institut Armand Frappier, Laval, Quebec, Canada. AD - Centre for Host-Parasite Interactions, Institut National de la Recherche Scientifique-Institut Armand Frappier, Laval, Quebec, Canada. FAU - Masvidal, Laia AU - Masvidal L AD - Department of Oncology-Pathology, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden. FAU - Aguirre, Maria AU - Aguirre M AD - Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada. FAU - Fonseca, Bruno D AU - Fonseca BD AD - Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada. FAU - van Kempen, Leon C AU - van Kempen LC AD - Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada. AD - Department of Pathology, McGill University, Montreal, Quebec, Canada. AD - Department of Pathology and Medical Biology, University Medical Centre, Groningen, The Netherlands. FAU - Alain, Tommy AU - Alain T AD - Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada. FAU - Larsson, Ola AU - Larsson O AD - Department of Oncology-Pathology, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden. FAU - Jaramillo, Maritza AU - Jaramillo M AUID- ORCID: 0000-0002-1910-5684 AD - Institut National de la Recherche Scientifique-Institut Armand Frappier, Laval, Quebec, Canada maritza.jaramillo@iaf.inrs.ca. AD - Centre for Host-Parasite Interactions, Institut National de la Recherche Scientifique-Institut Armand Frappier, Laval, Quebec, Canada. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180822 PL - United States TA - Infect Immun JT - Infection and immunity JID - 0246127 RN - 0 (Mitochondrial Proteins) RN - 0 (Protozoan Proteins) RN - EC 2.7.1.1 (mTOR protein, mouse) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Animals MH - Cells, Cultured MH - *Host-Parasite Interactions MH - Macrophages/*parasitology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Mitochondrial Proteins/genetics MH - Protein Biosynthesis/*genetics MH - Protozoan Proteins/immunology MH - RNA 5' Terminal Oligopyrimidine Sequence MH - Signal Transduction MH - TOR Serine-Threonine Kinases/genetics MH - Toxoplasma/*pathogenicity PMC - PMC6105892 OTO - NOTNLM OT - Toxoplasma gondii OT - host-pathogen interactions OT - mTOR OT - macrophages OT - translational control EDAT- 2018/07/04 06:00 MHDA- 2019/03/06 06:00 PMCR- 2019/02/22 CRDT- 2018/07/04 06:00 PHST- 2018/03/29 00:00 [received] PHST- 2018/06/22 00:00 [accepted] PHST- 2018/07/04 06:00 [pubmed] PHST- 2019/03/06 06:00 [medline] PHST- 2018/07/04 06:00 [entrez] PHST- 2019/02/22 00:00 [pmc-release] AID - IAI.00244-18 [pii] AID - 00244-18 [pii] AID - 10.1128/IAI.00244-18 [doi] PST - epublish SO - Infect Immun. 2018 Aug 22;86(9):e00244-18. doi: 10.1128/IAI.00244-18. Print 2018 Sep.