Proteomic profiles of Lissachatina (Heterobranchia) and Pomacea (Caenogastropoda) snails infected with Angiostrongylus cantonensis using 4D label-free quantitative analysis

Angiostrongylus cantonensis, the causative agent of human eosinophilic meningitis, utilizes terrestrial and freshwater gastropods as intermediate hosts. However, the molecular mechanisms underlying these host-parasite interactions remain unclear. We applied four-dimensional label-free quantitative (4D-LFQ) proteomics to examine proteomic alterations in infected versus uninfected specimens of two intermediate snail hosts, Lissachatina fulica and Pomacea canaliculata. Differentially expressed proteins (DEPs) were identified, followed by Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. In infected Lissachatina, 36 proteins were upregulated and 104 downregulated, while in infected Pomacea, 94 were upregulated and 364 downregulated. GO analysis revealed 111 enriched terms linked to 71 DEPs in Lissachatina and 484 terms associated with 389 DEPs in Pomacea. KEGG pathway enrichment (Level 3) showed predominant downregulation, including 12 of 20 pathways in Lissachatina and 18 of 20 in Pomacea. Both species shared downregulation in essential pathways: ribosome, proteasome, aminoacyl-tRNA biosynthesis (genetic information processing); glycolysis/gluconeogenesis, pyruvate metabolism, sulfur metabolism (metabolic); and phagosome formation and endocytosis (immune-related). Protein-protein association (PPA) analysis identified conserved hub proteins, Tr-type G domain and T-complex chaperonins, indicating coordinated disruption of translational and proteostatic processes in both groups. Our findings suggest that A. cantonensis can modulate host immunity and metabolism, suppressing key protective responses in both gastropod hosts. This proteomic data may serve as a foundation for discovering biomarkers and designing interventions to disrupt the parasite's life cycle.