|
| Status |
Public on Feb 15, 2019 |
| Title |
The Toxoplasma effector TEEGR promotes parasite persistence by modulating NF-κB signalling via EZH2 |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
The protozoan parasite Toxoplasma gondii has co-evolved with its homeothermic hosts (humans included) strategies that drive its quasi-asymptomatic persistence in hosts, hence optimizing the chance of transmission to new hosts. Persistence, which starts with a small subset of parasites that escape host immune killing and colonize the so-called immune privileged tissues where they differentiate into a low replicating stage, is driven by the interleukin 12 (IL-12)-interferon-γ (IFN-γ) axis. Recent characterization of a family of Toxoplasma effectors that are delivered into the host cell, in which they rewire the host cell gene expression, has allowed the identification of regulators of the IL-12-IFN-γ axis, including repressors. We now report on the dense granule-resident effector, called TEEGR (Toxoplasma E2F4-associated EZH2-inducing gene regulator) that counteracts the nuclear factor-κB (NF-κB) signalling pathway. Once exported into the host cell, TEEGR ends up in the nucleus where it not only complexes with the E2F3 and E2F4 host transcription factors to induce gene expression, but also promotes shaping of a non-permissive chromatin through its capacity to switch on EZH2. Remarkably, EZH2 fosters the epigenetic silencing of a subset of NF-κB-regulated cytokines, thereby strongly contributing to the host immune equilibrium that influences the host immune response and promotes parasite persistence in mice.
|
| |
|
| Overall design |
Human (HA and HFF) cells were left uninfected or infected for 24 hours with Pruku80, Pruku80ΔTEEGR or Pruku80ΔTEEGR+TEEGR (complemented) Toxoplasma type II strains before gene expression was measured. Three independent experiments were performed for each condition.
|
| |
|
| Contributor(s) |
Braun L, Brenier-Pinchart M, Hammoudi P, Cannella D, Kieffer-Jaquinod S, Vollaire J, Josserand V, Touquet B, Couté Y, Tardieux I, Bougdour A, Hakimi MA |
| Citation(s) |
31036909 |
| Submission date |
Apr 24, 2018 |
| Last update date |
May 17, 2019 |
| 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 (7)
|
|
| This SubSeries is part of SuperSeries: |
| GSE113658 |
The Toxoplasma effector TEEGR promotes parasite persistence by modulating NF-κB signalling via EZH2 |
|
| Relations |
| BioProject |
PRJNA453540 |
Less...
More...