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Mem Inst Oswaldo Cruz, Rio de Janeiro, VOLUME 121 | 2026

Research Articles

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

Alex Martins Nasaré¹, Roberto Carlos Tedesco², Paula Andrea Faria Waziry³, Lorena de Paula Pantaleon⁴, Esther Lopes Ricci⁴, Luís Antônio Baffile Leoni⁵, André Rinaldi Fukushima^6,+, Andres Jimenez Galisteo Junior¹

¹Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Laboratório de Investigação Médica em Protozoologia, Bacteriologia e Resistência Antimicrobiana-LIM-49, São Paulo, SP, Brasil
²Universidade Federal de São Paulo, São Paulo, SP, Brasil
³Florida Atlantic University, Schmidt College of Science, Boca Raton, FL, USA
⁴Universidade Presbiteriana Mackenzie, São Paulo, SP, Brasil
⁵Universidade Santo Amaro, São Paulo, SP, Brasil
⁶Universidade de São Paulo, Faculdade de Ciências da Saúde, São Paulo, SP, Brasil

DOI: 10.1590/0074-02760250141

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ABSTRACT

BACKGROUND 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.
OBJECTIVES To investigate whether RPE cells actively drive macrophage migration during T. gondii infection in vitro, and to identify associated cytokine profiles.
METHODS 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.
FINDINGS 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).
MAIN CONCLUSIONS 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.

key words: ocular toxoplasmosis retinal pigment epithelium macrophages cell movement cytokines Toxoplasma gondii

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