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

infection (Homma et al., 2014a) . Notably, Tlr3, Ddx58/ RIGI, Ifih1/MDA5 and Irf7, which are innate immune genes of the upstream signalling pathway relating to I-IFN induction, were suppressed by prion infection (Supplementary Fig. 1 ). IRF3 can contribute to the regulation of gene expression not only for Ifnb but also for Ifih1/ MDA5 (Yount et al., 2007) . TLR3 (Heinz et al., 2003) , IRF1 (Choi et al., 2009) and IRF7 (Farlik et al., 2012) are evoked by STAT1 and NFB is activated by intracellular signalling in response to IFN-b stimuli. Moreover, IRF1 is a transcription factor that positively regulates RIGI expression in human cells (Su et al., 2007) . These studies indicate that prion infection might result in a dysfunctional immune system following the suppression of the expression of several genes by IRF3 reduction because type I IFN signalling mediated by IRF3 is closely connected with the regulation of expression of several innate immunity-related genes. However, the mechanism of action has not yet been determined and needs to be investigated in the future.