Teresa Cruz-Bustos Teresa Cruz-Bustos Anna Sophia Feix Anna Sophia Feix Karin Hummel Karin Hummel Sarah Schlosser Sarah Schlosser Ebrahim Razzazi-Fazeli Ebrahim Razzazi-Fazeli Anja Joachim Anja Joachim Fronteirs Media Sa 2025 Extracellular vesicles (EVs) are emerging as powerful tools used by pathogens to manipulate host cells, delivering molecular cargo that rewires cellular processes and the immune response. Toxoplasma gondii, a globally distributed parasite capable of infecting nearly all nucleated animal cells, uses this strategy to thrive in diverse host species and tissue environments. Here, we reveal the adaptability of T. gondii EVs through proteomic analysis of vesicles released from tachyzoites cultured in four different host cell types: human fibroblasts, green monkey kidney epithelial cells, mouse myoblasts and porcine intestinal epithelial cells.A core set of 1,244 proteins was consistently identified across TgEVs, defining a conserved signature. Beyond this conserved cargo, host-cell specific variation revealed how T. gondii fine-tunes EV content to exploit different cellular environments. Functional enrichment analyses revealed roles for TgEVs in targeting host protein synthesis and stress response pathways, with implications for immune evasion and infection spread.These findings provide insight into the potential role of EVs in host-pathogen interactions and help us understand the adaptive strategies used by T. gondii to survive and spread. PDFDocument eng 2025-04-17T08:19:57.721762Z 2025 Toxoplasma Metabolism Extracellular Vesicles Metabolism Animals Humans Mice Proteomics Swine Chlorocebus Aethiops Host-Pathogen Interactions Fibroblasts Parasitology Fibroblasts Metabolism Epithelial Cells Parasitology Epithelial Cells Metabolism Cell Line Toxoplasmosis Metabolism Toxoplasmosis Parasitology Host-Parasite Interactions Proteome 12440120 b application/pdf http://creativecommons.org/licenses/by/4.0/