Fig. 5: Hepaciviral infection in mouse and human induce intrahepatic lymphoid structures with highly similar cellular composition, organizational microarchitecture and cell–cell contacts.

a,b, Xenium Prime 5K spatial transcriptomics of liver tissue from healthy, AIH, HBV-infected and HCV-infected humans with upstream staining (a) and selected transcript localization (b). c–g, Quantitative analyses from spatial transcriptomics demonstrating number of leukocytic aggregates per mm² of tissue (c), aggregate area of leukocytic aggregates (d), and lymphocytic cell-type proportions of B cells (e), CD4⁺ T cells (f) and CD8⁺ T cells (g) observed in leukocytic aggregates from individuals with AIH (n = 1), chronic HBV (n = 2) and chronic HCV (n = 2) infection. Data are mean + s.e.m. d–g, One-way ANOVA with Tukey’s multiple comparisons test. AIH versus HBV: P = 0.0101 (g). h, Quantification of cell types and their direct contact partners within leukocytic aggregates from annotated spatial transcriptomics with subcellular resolution and cell segmentation during mouse RHV (orange) and human HCV (blue) infection. HSC, hepatic stellate cell. i–n, RHV-infected mouse liver (i,k,m) and HCV-infected human liver (j,l,n) tissue. Generative GC-like structures were characterized upstream staining (i,j) and GC-associated transcript localization (k,l) and colour-coded cell-type annotation with selected overlaid transcripts (m,n). o–t, RHV-infected mouse liver (o,q,s) and HCV-infected human liver (p,r,t) tissue. Areas of intrahepatic plasma cell residency were characterized by upstream staining (o,p) and plasma cell and hepatic stellate cell and fibroblast-associated transcripts (q,r) with colour-coded cell-type annotation (s,t). Based on similar morphological H&E staining with limited interindividual variability of n = 2 HCV-infected humans and n = 4 RHV-infected mice, Xenium 5K was performed on tissue from n = 2 human and n = 1 mouse livers, from which n = 1 representative tissue of each are shown in i–t.

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