Figure 9.
ZNRF1 protects mice from S. aureus superinfection induced by antiviral immunity. (A) RT-qPCR analysis of the expression of Ifnb, Ifnl2, and Ifnl3 in BMDMs from Znrf1+/+ and Znrf1−/− mice after poly(I:C) (30 μg/ml) stimulation for 4 h. (B–F) Znrf1+/+ and Znrf1−/− mice were administered poly(I:C) (2.5 mg/kg) or saline i.t. daily for 6 d. (B and C) RT-qPCR analysis of the mRNA expression of type I and III IFNs and p53-dependent antiproliferative genes in lung tissue from Znrf1+/+ and Znrf1−/− mice. (D) Znrf1+/+ and Znrf1−/− mice administered poly(I:C) (2.5 mg/kg) i.t. for 6 d were infected i.t. with 4 × 107 CFU of S. aureus and monitored for survival. (E–G) Mice administered poly(I:C) (2.5 mg/kg) i.t. for 6 d were i.t. infected with 5 × 107 CFU of S. aureus. Mice were sacrificed 18 h after infection. (E) H&E staining of histological sections of lung tissues. Objective magnification, ×4 and ×20. Scale bars, 1,000 and 200 μm, respectively. (F) IFN-λ3 protein levels from lung homogenates were evaluated by ELISA. (G) Lung bacterial burdens normalized by lung homogenates were determined by colony-forming assay. *P < 0.05, **P < 0.01, and ***P < 0.001 (Student’s t test). Data are representative of three independent experiments (error bars, mean ± SD). Log-rank (Mantel-Cox) test, corrected for multiple comparisons, was performed to monitor survival in D.