Host genetic regulation of immune tolerance and disease persistence in human echinococcosis

Human echinococcosis, caused by Echinococcus spp., remains a significant public health concern in endemic regions and manifests primarily as cystic echinococcosis (CE) and alveolar echinococcosis (AE), both characterized by chronic infection and heterogeneous clinical outcomes. This review synthesizes current evidence on host genetic determinants that influence immune responses, susceptibility, and disease persistence in CE and AE. Available studies indicate that polymorphisms in genes encoding key immunoregulatory cytokines, particularly IL10 and TGFB1, are associated with an anti-inflammatory immune profile that favors parasite persistence through enhanced regulatory activity and suppression of protective effector responses. Cytokine pathways involving IL-4, IL-13, and IFN-γ further modulate the balance between Th2-mediated and Th1-mediated immune responses, thereby influencing infection outcomes. In addition, innate immune pathways, including Toll-like receptor signaling, affect early parasite recognition and downstream immune responses, although direct human genetic evidence for Toll-like receptor polymorphisms in CE and AE remains limited. Human leukocyte antigen class II polymorphisms may also contribute to inter-individual differences in antigen presentation and CE susceptibility, although reported associations remain population-specific and require further validation. Collectively, these findings support a mechanistic framework in which host immunogenetic variation shapes the balance between immune activation and tolerance and may influence disease trajectory. Integration of genetic markers with clinical and imaging data may improve risk stratification and support the development of more targeted therapeutic strategies. Future research should prioritize large-scale, multicenter studies, standardized phenotyping, and functional validation to clarify the clinical relevance of identified variants.