Figure 6.

Non-hematopoietically Derived Type I Interferon Signals to IFNAR1 Expressed on Hepatocytes and Causes Liver Pathology

(A) Serum levels of IFN-α (n = 6 mice) and ALT (n = 10 or 11 mice pooled from three independent experiments) of WT→Sod1^−/− and Irf7^−/−→Sod1^−/− chimeric mice 24 hr after infection with LCMV.

(B) IFN-α and (C) ALT of Sod1^−/− mice infected with LCMV upon treatment with liposomal clodronate or empty liposomes (n = 4 mice per group). One out of ≥ two similar experiments is shown.

(D and E) WT and Ifnar1^−/− mice were infected with LCMV. Levels of (D) serum ALT and (E) Atf3 mRNA in the liver were measured at 42 hr after infection (D and E, n = 4 mice). One out of ≥ two similar experiments is shown.

(F) WT and Stat1^−/− mice were infected with LCMV and levels of serum ALT (n = 4 mice) were measured. One out of ≥ two similar experiments is shown.

(G) Sod1 mRNA (n = 4–9 mice pooled from three experiments) in the liver were measured at 42 hr after infection.

(H) WT, Sod1^−/− and Stat1^−/−Sod1^−/− mice were infected with LCMV and levels of serum ALT were measured (n = 4 mice per group).

(I) WT→WT, WT→Ifnar1^−/−, and WT→Stat1^−/− chimeric mice were infected with LCMV and levels of serum ALT at 36–39 hr after infection were measured (n = 8 mice pooled from two experiments).

(J and K) WT mice, Cre-Alb ERT2 x Ifnar1^fl/WT or Cre-Alb ERT2 x Ifnar1^WT/WT (designated as Cre-Alb ERT2 × Ifnar1^WT in the graph) and Cre-Alb ERT2 x Ifnar1^fl/fl mice were administered 1 mg tamoxifen in sunflower oil i.p. each for 5 consecutive days, subsequently infected with LCMV and (J) levels of serum ALT and (K) viral loads in the liver 72 hr after infection were measured (n = 4 or 5 mice per group).

Statistical significance was calculated by unpaired t test (A and G), two-way (B–D, F, H, J) or one-way (E, I, and K) ANOVA with Bonferroni correction. Symbols and bars represent the mean ± SEM.