|
| Status |
Public on Jul 18, 2016 |
| Title |
Toxoplasma gondii TgIST co-opts host chromatin repressors dampening STAT1-dependent gene regulation and IFN-γ-mediated host defenses. |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
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 contribute 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.
|
| |
|
| Overall design |
HFF, 2fTGH (STAT1+/+) and U3A (STAT1-/-) human cells were left uninfected or infected for 24 hours with 76KGFP and 76KGFPΔTgIST Toxoplasma strains and stimulated with 100 U/ml IFN-γ for 6 hours before gene expression was measured. Three independent experiments were performed for each condition.
|
| |
|
| Contributor(s) |
Gay G, Braun L, Brenier-Pinchart M, Vollaire J, Josserand V, Bertini R, Varesano A, Touquet B, De Bock P, Coute Y, Tardieux I, Bougdour A, Hakimi MA |
| Citation(s) |
27503074 |
| Submission date |
May 18, 2016 |
| Last update date |
Jan 09, 2018 |
| Contact name |
Mohamed-ali HAKIMI |
| E-mail(s) |
mohamed-ali.hakimi@univ-grenoble-alpes.fr
|
| Phone |
(33)476637469
|
| Organization name |
CNRS
|
| Department |
UMR5309
|
| Lab |
IAB - HAKIMI Team
|
| Street address |
Domaine de la Merci, Campus Santé
|
| City |
LA TRONCHE |
| State/province |
Grenoble |
| ZIP/Postal code |
38700 |
| Country |
France |
| |
|
| Platforms (1) |
| GPL13497 |
Agilent-026652 Whole Human Genome Microarray 4x44K v2 (Probe Name version) |
|
| Samples (9)
|
|
| Relations |
| BioProject |
PRJNA322077 |
Less...
More...