The Protozoan Parasite Toxoplasma gondii Selectively Reprograms the Host Cell Translatome

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*

*Corresponding author voor dit werk

    OnderzoeksoutputAcademicpeer review

    21 Citaten (Scopus)
    290 Downloads (Pure)

    Samenvatting

    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.

    Originele taal-2English
    ArtikelnummerARTN e00244-18
    Aantal pagina's20
    TijdschriftInfection and Immunity
    Volume86
    Nummer van het tijdschrift9
    DOI's
    StatusPublished - sep.-2018

    Vingerafdruk

    Duik in de onderzoeksthema's van 'The Protozoan Parasite Toxoplasma gondii Selectively Reprograms the Host Cell Translatome'. Samen vormen ze een unieke vingerafdruk.

    Citeer dit