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The Protozoan Parasite Toxoplasma gondii Selectively Reprograms the Host Cell Translatome

Leroux, L-P., Lorent, J., Graber, T. E., Chaparro, V., Masvidal, L., Aguirre, M., Fonseca, B. D., van Kempen, L. C., Alain, T., Larsson, O. & Jaramillo, M., Sep-2018, In : Infection and Immunity. 86, 9, 20 p., ARTN e00244-18.

Research output: Contribution to journalArticleAcademicpeer-review

  • Louis-Philippe Leroux
  • Julie Lorent
  • Tyson E. Graber
  • Visnu Chaparro
  • Laia Masvidal
  • Maria Aguirre
  • Bruno D. Fonseca
  • Léon C. van Kempen
  • Tommy Alain
  • Ola Larsson
  • Maritza Jaramillo

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.

Original languageEnglish
Article numberARTN e00244-18
Number of pages20
JournalInfection and Immunity
Volume86
Issue number9
Publication statusPublished - Sep-2018

    Keywords

  • Toxoplasma gondii, host-pathogen interactions, mTOR, macrophages, translational control, PARASITOPHOROUS VACUOLE MEMBRANE, MESSENGER-RNA TRANSLATION, PROTEIN-SYNTHESIS, DIFFERENTIAL TRANSLATION, POLY(A)-BINDING PROTEINS, ENDOPLASMIC-RETICULUM, MAMMALIAN-TARGET, IMMUNE-RESPONSES, DENDRITIC CELLS, INNATE IMMUNITY

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