Toxoplasmosis is a globally significant infectious disease, affecting approximately one‐third of the world’s population. Ocular toxoplasmosis (OT) is a major and vision‐threatening clinical manifestation. However, its pathogenesis remains elusive, and effective targeted therapies are unavailable. This study demonstrates that Toxoplasma gondii infection induces epithelial‐mesenchymal transition (EMT)‐like changes in both human retinal pigment epithelial (RPE) cells (ARPE‐19) and murine ocular tissues. Mechanistic investigations, employing rhoptry protein 16 (ROP16) knockout parasites and ROP16 overexpression models, revealed that the parasite‐derived protein ROP16 promotes EMT‐like changes by activating the host signal transducer and activator of transcription 3 (STAT3) and transforming growth factor β1 (TGF‐β1) signaling pathway. Furthermore, pharmacological inhibition of STAT3 or TGF‐β1 significantly attenuated EMT‐like changes in vitro and ameliorated OT pathology in mice. In summary, our findings identify the ROP16‐STAT3 and TGF‐β1 pathways as a key regulatory pathway in OT pathogenesis, providing novel insights into the disease mechanism and suggesting STAT3 and TGF‐β1 inhibitors as promising therapeutic candidates.
Song et al. (Thu,) studied this question.