Extended Data Fig. 9: tDC promote immune pathology following M-CoV infection.
a TCF4cKO vs TCF4control mice were generated by transplanting Itgax-Cre+/− Tcf4fl/fl or Itgax-Cre−/− Tcf4fl/fl BM into lethally irradiated CD45.1 WT mice, respectively. 2 months post-reconstitution, mice were infected with M-CoV, and the frequency of liver DC (mean + SD) analyzed 2-days later (n = 6 mice/group in 2 experiments). b Percentage weight loss (left, mean + SD) and survival (right) of TCF4cKO (n = 7) vs TCF4control (n = 10) mice in 3 experiments. c As in (b), but viral titers (log10 pfu/gr. tissue) were determined 5-days post-M-CoV infection. N = 7 mice for TCF4control and n = 6 mice for TCF4cKO. Violin plots show distribution from 3 experiments. d As in (b), but shown is serum ALT (mean + SD; n = 6 mice/group in 3 experiments). e Serum cytokines were determined by Luminex in control (n = 7 mice), pDCΔ (n = 8) and pDCΔtDCΔ (n = 8) 2-days p.i. in 4 experiments. Shown are cytokines different between pDCΔ vs pDCΔtDCΔ mice. f Percentage weight loss (left, mean + SD) and survival (right) of pDCΔ mice inoculated with anti-NK1.1 Ab or isotype control on day −1, 0 and 2 post-infection with M-CoV. N = 3 mice/group except n = 5 mice for pDCΔ + isotype, pooled from 2 experiments. g As in (f), but viral titers were evaluated at 5-days p.i. (n = 3 mice/group). Violin plots show distribution from 2 experiments. h As in Fig. 8j, but splenic viral titers (log10 pfu/gr. tissue) were determined. N = 5 mice/group except n = 8 for pDCΔ + control Ab. Violin plots show distribution from 2 experiments. i As in Fig. 8k but heatmaps show secretion of TNF, IL-6 and IL-12p70 by DC subsets (N = 4 mice/subset in 4 experiments). Statistical differences were determined by unpaired two-tailed t-test (a,c-d), One-way ANOVA (e,h) or Two-way ANOVA (b,f) with Tukey’s multiple comparisons test, and Mantel-Cox test for survival (b,f).
