Alveolar echinococcosis drives functional reprogramming of hepatic CD8⁺ T cells

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.

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).

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.

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.