Type I interferon protects neurons from prions in in vivo models

Ishibashi, Daisuke; Homma, Takujiro; Nakagaki, Takehiro; Fuse, Takayuki; Sano, Kazunori; Satoh, Katsuya; Mori, Tsuyoshi; Atarashi, Ryuichiro; Nishida, Noriyuki

Prion infection suppressed Ifnb gene expression in 22 Lprion infected cells, and the level of Ifnb expression recovered following reduction of PrP Sc by treatment with anti-prion compound and antibody (Fig. 1) . This suppression of Ifnb gene transcription was followed by the low expression of IRF3 via a reduction of Oct-1 after prion Figure 4 Ifnar1 gene depletion is susceptible to prion infection in in vivo animal models. (A-D) Evaluation of prion pathogenesis in IFNAR1 À/À mice. (A) Survival curves in wild-type ( + / + ) and Ifnar1 À/À (À/À) mice following inoculation intracerebrally (i.c.) with a 10 À1 dilution of 22 L-brain homogenate (P 5 0.001, log-rank test). PrP Sc levels (B) and histological changes (C) in the brain at 100 dpi and in terminal phase of prion infection. (C) Panels show vacuolation (HE), microglia (IBA1), and astrocytes (GFAP) in the cortex (Cx), and PrP Sc deposits in cortex and spleen. Scale bars = 50 mm. (D) Lesion profiles of vacuolation, microgliosis, astrogliosis, and PrP Sc deposits in the same five brain regions: cortex, hippocampus (Hi), thalamus (Th), cerebellum (Ce), and pons (Po). Details of the lesion severity score for each histological change are described in the 'Materials and methods' section. Circle and triangle symbols indicate wild-type and Ifnar1 À/À mice, respectively, at 100 dpi (black) and in the terminal stage (red). *P 5 0.05, **P 5 0.01 versus wild-type mice at 100 dpi. Error bars represent SEM. Statistical significance was determined using unpaired Student's t-test (D). Results represent at least three independent experiments.