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Infect Immun. 2018 Aug 22;86(9). pii: e00244-18. doi: 10.1128/IAI.00244-18. Print 2018 Sep.

The Protozoan Parasite Toxoplasma gondii Selectively Reprograms the Host Cell Translatome.

Author information

1
Institut National de la Recherche Scientifique-Institut Armand Frappier, Laval, Quebec, Canada.
2
Centre for Host-Parasite Interactions, Institut National de la Recherche Scientifique-Institut Armand Frappier, Laval, Quebec, Canada.
3
Department of Oncology-Pathology, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.
4
Children's Hospital of Eastern Ontario Research Institute, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
5
Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada.
6
Department of Pathology, McGill University, Montreal, Quebec, Canada.
7
Department of Pathology and Medical Biology, University Medical Centre, Groningen, The Netherlands.
8
Institut National de la Recherche Scientifique-Institut Armand Frappier, Laval, Quebec, Canada maritza.jaramillo@iaf.inrs.ca.
#
Contributed equally

Abstract

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.

KEYWORDS:

Toxoplasma gondii; host-pathogen interactions; mTOR; macrophages; translational control

PMID:
29967092
PMCID:
PMC6105892
DOI:
10.1128/IAI.00244-18
[Indexed for MEDLINE]
Free PMC Article

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