Abstract: ObjectiveTo investigate the functional changes of dendritic cells（DCs) in patients at different stages of hepatitis B virus (HBV) infection and analyze the mechanisms underlying DC dysfunction. Methods Single-cell RNA sequencing dataset GSE182159 was downloaded from the GEO database and classified into healthy control (HC)，immune active (IA)，and immune tolerant （IT)groups based on infection stage. Peripheral blood samples were collected from 7 IA patients，7 IT patients，and 12 healthy controls.Flow cytometry was used to isolate classical dendritic cells（cDC)and plasmacytoid dendritic cells（pDC). The expression levels of transcription factors in cDC and pDCwere measured by quantitative real-time PCR （qRT-PCR). Bioinformatics analyses were performed using R and Python package. ResultsThe proportions of DCs in IA and IT groups were higher than that in HC group. Functional enrichment analysis revealed that the dfferentially expressed genes (DEGs) of cDCs in the IA group were primarily enriched for the processes,such as inflammatory response,MHCclass II antigenprocessing andpresentation，cell migration，signal transduction,metabolism, and immune response. In contrast the IT group exhibited lower enrichment intensity and a significant reduction in interferon responses. The DEGs of pDC in the IA group were enriched in the processes of MHC-II antigen presentation,Fc receptor signal transduction, and metabolism,whereas those in the IT group were showed enrichment only in Fc receptor signal transduction and metabolismwithalower intensity.Bothgroupsexhbitedreducedsynthesisof typesIandIinteferonsinpDCwiththeITgroupshowing a more pronounced downregulation. Cell-cell communication analysis demonstrated enhanced interactions between myeloid cells（except pDC) and T cells in the IA group, whereas the interactions between cDC/pDC and T cells in the IT group were reduced. Transcription factor analysis revealed that STAT2,STAT3, IRFl, and IRF5 were highly expressed in the IAgroup but their expression exhibited lower expression levels in the IT group. In contrast, BHLHE4O was broadly upregulated in both cDC and pDC subsets within the IT group.The qRT-PCR results were consistent with the findings from the single-cell transcription factor analysis. ConclusionThe IT phase of hepatitis B infectionrepresents acritical period for cDCdysfunction,characterized bysignificantsuppression of MHcI antigen presentation,metabolism,and interferon responsiveness. The functional impairment of pDC precedes that of cDC，as evidenced by a marked downregulation of interferon synthesiscapacityobserved during the IAphase.