Resveratrol modulates inflammatory gene expression in Toxoplasma gondii-infected microglia and shows structurally plausible interactions with parasite virulence proteins.

Microglia represent one of the mechanisms by which the parasite enters in the brain and contributes to inflammatory responses during infection. P2X7 receptor, NLRP3 inflammasome, and other inflammatory markers are elevated in toxoplasmosis, while resveratrol has demonstrated anti-inflammatory and antiparasitic potential. This study investigated resveratrol on the P2X7/NLRP3 pathway (in vitro) and explored potential interactions with ROP18 and AMA1 proteins of Toxoplasma gondii (in silico). BV-2 microglial cells were exposed to different RH strain parasite-to-cell ratios and infection times to determine susceptibility. Cells were infected (3:1 - cell:parasite, 3 h) and treated with resveratrol (0.1-50 μM, 2 h). DNA release, reactive oxygen species, nitric oxide, cell-cycle distribution, and expression of inflammatory genes, including P2X7 and NLRP3, were assessed. In silico analyses predicted potential interactions between resveratrol and ROP18 and AMA1. BV-2 cells were highly susceptible to infection, with infection-associated cellular alterations varying according to parasite concentration and exposure time, as reflected by NO levels and monolayer disruption. Resveratrol treatment was associated with partial restoration of metabolic activity, reduced ROS and NO levels, modulation of cell-cycle distribution, decreased expression of IL-1β, TNF-α, and IFN-γ, and increased IL-10 expression. Infection-induced upregulation of NLRP3, Caspase-1, and purinergic receptors (P2X7, A2A) at the transcriptional level was attenuated by resveratrol, especially at 1 and 10 μM. In silico analyses suggest structurally plausible interactions between resveratrol and the ROP18 and AMA1 proteins. These findings suggest that RSV may represent a promising candidate for modulation of inflammation-related transcriptional responses during neurotoxoplasmosis.