Fig. 4.

Fatal inflammation in TLR9^TM-expressing neonates requires IFN-γ receptor signaling but not type I IFN signaling. (A) Survival curves of TLR9^fsTM/+β-actin-cre⁺Ifnar1^−/− neonates. Results are combined from multiple litters and analyzed using the logrank (Mantel–Cox) test. (B) LSK and Ly6C^hi monocyte cell populations do not expand in TLR9^fsTM/+β-actin-cre⁺Ifngr1^−/− neonates. Quantification of LSK and Ly6C^hi monocytes from neonatal livers of indicated genotypes (combined from multiple litters) is shown as mean ± SEM and analyzed using one-way ANOVA with Tukey’s multiple comparisons posttest. Mouse numbers: TLR9^fsTM/+ β-actin-cre^–, n = 4; TLR9^fsTM/+ β-actin-cre⁺, n = 5; TLR9^fsTM/+β-actin-cre^–Ifnar1^+/+, n = 4; TLR9^fsTM/+β-actin-cre⁺Ifnar1^+/−, n = 4; TLR9^fsTM/+β-actin-cre⁺Ifnar1^−/−, n = 3; TLR9^fsTM/+β-actin-cre^–Ifngr1^+/−, n = 4; TLR9^fsTM/+β-actin-cre⁺Ifngr1^+/−, n = 7; TLR9^fsTM/+β-actin-cre⁺Ifngr1^−/−, n = 9. (C) Quantitative PCR analysis of inflammatory genes in TLR9^fsTM/+β-actin-cre⁺ neonatal livers. Data are representative of two independent experiments and presented as fold change of expression in TLR9^fsTM/+β-actin-cre⁺ vs. TLR9^fsTM/+ β-actin-cre^–. Bars show mean ± SD; statistics calculated using the two-tailed Student’s t test. (D) Survival curves of TLR9^fsTM/+β-actin-cre⁺Ifngr1^−/− neonates. Results are combined from multiple litters and analyzed using the logrank (Mantel-Cox) test. In all panels, *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.