Skip to Main content Skip to Navigation

Subversion de la réponse immune de l'hôte par Toxoplasma gondii

Abstract : An early hallmark of Toxoplasma gondii infection is the rapid control of the parasite population by a potent multifaceted innate immune response that engages resident and homing immune cells along with pro- and counter-inflammatory cytokines. In this context, IFN-γ activates a variety of T. gondii–targeting activities in immune and nonimmune cells but can also con- tribute to host immune pathology. T. gondii has evolved mechanisms to timely counteract the host IFN-γ defenses by interfering with the transcription of IFN-γ–stimulated genes. We now have identified TgIST (T. gondii inhibitor of STAT1 transcriptional activity) as a critical molecular switch that is secreted by intracellular parasites and traffics to the host cell nucleus where it inhibits STAT1-dependent proinflammatory gene expression. We show that TgIST not only sequesters STAT1 on dedicated loci but also promotes shaping of a nonpermissive chromatin through its capacity to recruit the nucleosome remodeling deacetylase (NuRD) transcriptional repressor. We found that during mice acute infection, TgIST-deficient parasites are rapidly eliminated by the homing Gr1+ inflammatory monocytes, thus highlighting the protective role of TgIST against IFN-γ–mediated killing. By uncovering TgIST functions, this study brings novel evidence on how T. gondii has devised a molecular weapon of choice to take control over a ubiquitous immune gene expression mechanism in metazoans, as a way to promote long-term parasitism.
Document type :
Complete list of metadatas

Cited literature [254 references]  Display  Hide  Download
Contributor : Abes Star :  Contact
Submitted on : Monday, February 4, 2019 - 4:53:32 PM
Last modification on : Tuesday, October 6, 2020 - 8:46:02 AM


Version validated by the jury (STAR)


  • HAL Id : tel-02006607, version 1



Gabrielle Gay. Subversion de la réponse immune de l'hôte par Toxoplasma gondii. Médecine humaine et pathologie. Université Grenoble Alpes, 2018. Français. ⟨NNT : 2018GREAV029⟩. ⟨tel-02006607⟩



Record views


Files downloads