Alveolar echinococcosis drives functional reprogramming of hepatic CD8+ T cells

Background Alveolar echinococcosis (AE), caused by the larval stage of Echinococcus multilocularis , exhibits infiltrative, tumor-like behavior in the liver and persists within its tolerogenic immune environment. Although T cells are central to host defense, the stage-specific remodeling of their lineage states during AE remains unclear. Methods A secondary AE infection model was established by portal vein injection of approximately 1,000 viable protoscoleces in C57BL/6 mice. Liver tissues collected at 3 days (3 dpi) and 3 months (3 mpi) post-infection were analyzed using single-cell RNA sequencing (scRNA-seq), flow cytometry, and multiplex immunofluorescence to characterize T-cell subset composition, transcriptional programs, and potential interactions with dendritic cells (DCs). Results scRNA-seq of 78,290 high-quality cells identified 13 immune and non-immune populations and revealed strong temporal shifts in hepatic immunity. Early infection featured macrophage-driven inflammation with reduced T-cell proportions, whereas late infection showed marked expansion of both T cells and DCs. CD8 + T-cell profiling demonstrated the establishment of a diversified compartment composed of cytotoxic, effector-memory, and exhausted subsets. These subsets exhibited coordinated transcriptional remodeling, including upregulation of regulatory genes ( Btg1, Tnfaip3, Junb, Nr4a1 ) and downregulation of early-induced inflammatory and metabolic genes, indicating adaptation to sustained antigen exposure. Spatial imaging further revealed ring-like accumulation of CD11c + DCs around lesions with adjacent clustering of CD8 + T cells, and ligand–receptor analysis highlighted Thy1–Adgre5 as a prominent DC–T-cell interaction axis. Conclusions AE infection drives a transition from acute inflammation to chronic immune regulation through extensive lineage diversification and functional reprogramming of CD8 + T cells. Spatially organized DC–T-cell interactions likely contribute to maintaining a regulated yet immunologically active microenvironment, providing insights for targeting chronic-stage immune responses in AE.