Toxoplasma gondii GRA12 Inhibits the NF-ΚB Signaling Pathway by Targeting P65 and the IKK Complex.

BACKGROUND

The NF-κB signaling pathway plays a critical role in innate immune defense against infections. However, many pathogens secrete toxins or effectors into host cells to manipulate cellular functions for their survival and proliferation. Toxoplasma gondii is known to establish chronic infections by employing sophisticated immune evasion strategies. Dense granule (GRA) proteins are essential for the survival and pathogenesis of T. gondii.

METHODS

In this study, plasmid transfection, cell culture, luciferase reporter assay, quantitative PCR, and western blot were employed to identify T. gondii GRA proteins that regulate the NF-κB pathway.

RESULTS

We demonstrate that GRA12, a specific GRA protein, significantly inhibits NF-κB promoter activity and the transcriptional expression of key cytokines, including IL-6, IL-12, TNF-α, and IFN-β. Western blot analysis further revealed that GRA12 suppresses the activation of the IKK complex and p65. Moreover, GRA12 prevents the nuclear translocation of p65.

CONCLUSIONS

Our findings demonstrate that GRA12 is involved in immune evasion by inhibiting the NF-κB pathway, thereby facilitating T. gondii dissemination and infection.