Extended Data Fig. 2: Systemic infection of prolonged duration still does not induce locally generated humoral immunity and harbors virus and immature leukocyte aggregates confined to zone 3 with marked reduction of oxidative phosphorylation compared to early iHALT precursors.
From: iHALT unlocks liver functionality as a surrogate secondary lymphoid organ
(A, C) Total and (B, D) virus-specific ASCs were quantified in the liver at week 4 post-infection for (A, B) RHV and (C, D) LCMV clone 13 infection with (E, F) representative ELISpot images showing (A, B) representative and (C, D) pooled data from (A-D) n = 2 independent experiments. Mice were either untreated (WT) or splenectomized and treated with FTY720 prior to infection with treatment being maintained throughout (splX + FTY720 [D -1]). Virus localization was determined by viral transcript density for individual portal and central zones at week 1 post-infection during (G) RHV and (H) LCMV clone 13 infection from n = 10 portal and n = 10 central zone selections from a Xenium 5 K spatial transcriptomics run of n = 1 mouse liver per group. Transcript density of genes associated with oxidative phosphorylation usage were quantified in (I) portal zone hepatocyte regions and (J) immature lymphocytic clusters at week 1 post-infection. Following (K) upstream staining, (L-O) individual transcript localization was determined in the liver at week 1 post-infection. (A-D, G-J) Mean + SEM. (A-D, G-J) Two-tailed, unpaired t-tests were performed. (A) p = 0.9168, (B) p = 0.1987, (C) p = 0.0008, (D) p < 0.0001, (G) p = 0.0261, (H) p = 0.0282. Statistical significance was denoted as *=(p ≤ 0.05), **=(p ≤ 0.01), ***=(p ≤ 0.001), and ****=(p ≤ 0.0001).
