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The protozoan parasite Toxoplasma gondii selectively reprograms the host cell translatome

Leroux, Louis-Phillipe; Lorent, Julie; Graber, Tyson; Chaparro, Visnu; Masvidal Sanz, Laia; Aguirre, Maria; Fonseca, Bruno D.; van Kempen, Léon C.; Alain, Tommy; Larsson, Ola; Jaramillo, Maritza (2018). The protozoan parasite Toxoplasma gondii selectively reprograms the host cell translatome Infection and Immunity , vol. 86 , nº 9:e00244-18. p. 1-20. DOI: 10.1128/IAI.00244-18.

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Résumé

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.

Type de document: Article
Mots-clés libres: Toxoplasma gondii; host-pathogen interactions; mTOR; macrophages; translational control
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 08 août 2019 00:55
Dernière modification: 08 août 2019 00:55
URI: http://espace.inrs.ca/id/eprint/8139

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