Retinal pigment epithelium drives macrophage migration during Toxoplasma gondii infection in vitro

Ocular toxoplasmosis is a leading cause of infectious posterior uveitis worldwide. The retinal pigment epithelium (RPE), a key barrier and immunomodulatory layer in the eye, is directly targeted by Toxoplasma gondii during infection. However, its role in orchestrating the local immune response remains unclear.

To investigate whether RPE cells actively drive macrophage migration during T. gondii infection in vitro, and to identify associated cytokine profiles.

Adult retinal pigment epithelial cells (ARPE)-19 and primary RPE cells were exposed to tachyzoites, soluble antigens or conditioned supernatants. Macrophage migration was assessed using Transwell® and under-agar assays. Cytokines were quantified by cytometric bead array.

Both ARPE-19 and primary RPE exhibited chemotaxis toward parasite antigens (0.12 - 0.5 μg), and enhanced interleukin-6 (IL-6), IL-10 and tumor necrosis factor-α (TNF-α) secretion. Co-culture with RAW 264.7 macrophages further amplified cytokine production. Primary RPE from infected animals occluded 90% of Transwell® pores within 24h. IL-6 and IL-10 levels strongly correlated with migratory activity (r = 0.82 and 0.77, respectively).

RPE cells are not passive targets but active participants in the ocular immune response to T. gondii. By secreting IL-6 and IL-10, they establish a chemotactic environment that recruits macrophages. These insights identify the RPE-cytokine-macrophage axis as a potential therapeutic target in ocular toxoplasmosis.