The effects of E. granulosus protoscoleces proteins on host immune cells were elucidated through transcriptomic and metabolomic analyses.

Echinococcus granulosus（E. granulosus） protoscoleces (PSCs) critically modulate host immune evasion through complex immunometabolic mechanisms that remain poorly characterized. This study integrates transcriptomic, metabolomic, and immunological analyses to dissect PSCs proteins-driven immunomodulation. Immunofluorescence and CCK-8 assays revealed concentration-dependent inhibition of lymphocyte viability by PSCs proteins, with low/medium concentrations selectively enhancing IL-9 and IL-4 secretion, while sustained TGF-β upregulation correlated with dosage escalation. Transcriptomic profiling identified 1840 differentially expressed genes (DEGs), enriched in phenylalanine metabolism and immunometabolic pathways (KEGG/GO), alongside metabolomic detection of 12 perturbed metabolites, implicating pyrimidine biosynthesis and bilirubin-mediated oxidative stress suppression. Multi-omics integration exposed a coordinated metabolic-gene network: PSCs proteins suppressed PI3K-Akt signaling while activating Th9 cytokine axes (IL-9/IL-4-TGF-β), driving immunometabolic reprogramming characterized by nucleotide salvage pathway activation and antioxidant defense attenuation. These cascades collectively remodeled an immune-tolerant microenvironment, facilitating parasite persistence. Our findings systematically delineate how PSCs proteins subvert host defenses via multi-target immunometabolic crosstalk, proposing novel therapeutic strategies targeting pyrimidine metabolism or cytokine networks to disrupt parasitic immune evasion in cystic echinococcosis.