Toxoplasma gondii GRA12 Inhibits the NF-ΚB Signaling Pathway by Targeting P65 and the IKK Complex
Meiling Ou1,2, Xiaowen Fang1, Ying Yuan1
1Department of Pathogen Biology, School of Medicine, Jinan University, Guangzhou 510632, China.
Genes
|May 4, 2026
Summary
Toxoplasma gondii GRA12 protein inhibits the NF-κB pathway, a key immune defense. This immune evasion mechanism helps the parasite spread and establish chronic infections.
Area of Science:
- Immunology
- Parasitology
- Molecular Biology
Background:
- The NF-κB signaling pathway is crucial for innate immunity against pathogens.
- Pathogens like *Toxoplasma gondii* use effector proteins to evade host immune responses.
- Dense granule (GRA) proteins are vital for *T. gondii* survival and pathogenesis.
Purpose of the Study:
- To identify *Toxoplasma gondii* GRA proteins that modulate the NF-κB signaling pathway.
- To investigate the role of specific GRA proteins in immune evasion.
Main Methods:
- Plasmid transfection and cell culture techniques.
- Luciferase reporter assays to measure promoter activity.
- Quantitative PCR and Western blot for gene and protein expression analysis.
Main Results:
- *Toxoplasma gondii* GRA12 protein significantly inhibits NF-κB promoter activity.
- GRA12 suppresses the expression of key immune cytokines (IL-6, IL-12, TNF-α, IFN-β).
- GRA12 blocks IKK complex and p65 activation and prevents p65 nuclear translocation.
Conclusions:
- GRA12 is an immune evasion factor for *Toxoplasma gondii*.
- By inhibiting the NF-κB pathway, GRA12 facilitates parasite dissemination and infection.
- Targeting GRA12 could be a strategy to combat *T. gondii* infections.
Related Concept Videos
02:26NF-κB-dependent Signaling Pathway
7.6K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.6K
02:26NF-kB-dependent Signaling Pathway
2.0K
2.0K
01:16TGF - β Signaling Pathway
7.2K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.2K
01:31The Intrinsic Apoptotic Pathway
6.2K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.2K
01:17The Extrinsic Apoptotic Pathway
6.2K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.2K
01:20The JAK-STAT Signaling Pathway
10.2K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
10.2K