Schistosomal extracellular vesicles: Mechanisms of immune modulation and emerging clinical applications

Schistosomiasis remains a persistent global health challenge and a leading cause of parasitic morbidity worldwide. The complex, enduring relationship between Schistosoma parasites and their human hosts is underpinned by a sophisticated molecular dialogue, much of which is mediated by extracellular vesicles (EVs). These parasite-derived vesicles, which carry proteins, lipids, and nucleic acids, act as a double-edged sword in host-parasite interactions. On one hand, they facilitate immune evasion by promoting Th2 polarization, expanding regulatory T cells, and driving alternative macrophage activation, thereby establishing an immunological milieu that favors parasite survival. On the other hand, these vesicles contribute to pathology by inducing granuloma formation, activating hepatic stellate cells, and advancing periportal fibrosis. Beyond their biological roles, schistosomal EVs harbor significant translational potential. Their unique, parasite-specific molecular signatures-principally microRNAs and surface tetraspanins-hold promise as biomarkers for sensitive, non-invasive diagnosis and prognostic monitoring of infection and related morbidity. Moreover, the immune-modulatory properties of these vesicles open new avenues for developing therapies, not only for schistosomiasis but also for inflammatory and autoimmune diseases. Harnessing EVs as multi-antigenic vaccine platforms or as engineered delivery systems represents a promising strategy to combat this neglected tropical disease. This narrative review integrates current knowledge on the biogenesis, composition, and diverse functions of schistosomal EVs, critically assesses their dual roles in immunomodulation and disease progression, and explores their emerging applications in diagnostics, therapeutics, and vaccine development, while addressing current challenges and future directions in this rapidly advancing field.