The particularities of the ocular immune environment and its barrier protection in the context of infection are not well elucidated. Toxoplasma gondii is one of the pathogens successfully crossing this barrier and establishing chronic infection in retinal cells. The establishment of this infection requires the modulation of the host ocular immune privilege in order to allow pathogen control while avoiding exacerbated inflammation. The ligand PD-L1 (CD274) is an immune checkpoint regulator and a key actor in the immune privilege by limiting T cell activity. Furthermore, IFN-β and IFN-λ play important roles in the outer blood-retinal barrier permeability and could also modulate the ocular immunomodulatory landscape, in addition to IFN-γ. To address these questions, we use confocal microscopy and transcriptomic approaches on a human in vitro model and a mouse model for the acute phase of ocular toxoplasmosis. Our first results show that T. gondii infection, but also secreted/excreted factors alter PD-L1 expression in human retinal pigment epithelial cells. We then confront these results with those obtained in our mouse model of PD-L1 expression and localization after types I and III interferon neutralization. These results will give us a better understanding of the interplay between T. gondii and the ocular immune privilege in order to find more targeted treatments for ocular toxoplasmosis.