There were main effects of disease (F = 43.96, df 1, 14, p < 0.0001) and of poly I:C (F = 79.41, df 1, 14, p < 0.0001) and an interaction of these two factors (F = 21.32, df 1, 14, p < 0.0005). Likewise, Mx1, assessed at the exon 2–exon
3 junction, showed an exaggerated induction in ME7 animals treated with poly I:C. There were main effects of disease (F = 7.70, df 1, 14, p < 0.05) and of poly I:C (F = 45.29, df 1, 14, p < 0.0001) and an interaction of these two factors (F = 5.87, df 1, 14, p < 0.05). Finally, PKR was more robustly induced by poly I:C in ME7 animals than in NBH animals. There were main effects of disease (F = 9.51, this website df 1, 14, p < 0.01) and of poly I:C (F = 55.12, df 1, 14, p < 0.0001), but
no significant interaction (F = 0.89, df 1, 14, p = 0.36) in this case. Thus, there is exaggerated type I IFN action in the CNS of ME7 animals challenged with poly I:C with respect to NBH animals similarly challenged. IL-10 was modestly induced by both poly I:C in normal animals (F = 34.97, df 1, 12, p < 0.0001) and by disease (main effect of disease: F = 28.32, df 1, 12, p = 0.0002) ( Fig. 6a). There was also an interaction of disease and poly I:C, ME7 + poly MK-2206 concentration I:C showing considerably more marked induction than all other groups (F = 22.23, df 1, 12, p = 0.0005). TREM2 (Fig. 6b) was markedly induced by disease (two-way ANOVA main effect of disease (F = 34.13, df 1, 12, p = 0.0001), and was slightly, but not significantly, affected by poly I:C (F = 4.49, df 1, 12, p = 0.0576). However there was a significant interaction between disease and poly I:C. TREM2 was Idelalisib concentration markedly more elevated in ME7 + poly I:C than in any other group (F = 5.32, df 1, 12, p = 0.0415). The expression of iNOS was
increased by poly I:C in NBH animals but was not increased by poly I:C in ME7 animals (Fig. 6c). As such, there were no main effects of disease or poly I:C but an interaction between these (F = 5.22, df 1, 14, p = 0.0385). The expression of MMP9 was very low and was not altered by any treatment (Fig. 6d). There were no statistically significant changes. IFNγ (Fig. 6e) was modestly increased in ME7 animals (main effect of disease, F = 21.34, df 1, 14, p = 0.0004) and decreased by poly I:C (main effect of poly I:C: F = 6.3, df 1, 14, p = 0.025). There was no interaction between these factors. Thus, in addition to reduced TNF-α expression (Fig. 3), there are further anti-inflammatory changes that appear to be selectively apparent in ME7 animals upon poly I:C treatment. Heightened expression of the signalling type I interferon receptor, IFNAR2 in ME7 animals (Fig. 6f) may contribute to this. IFNAR2 was induced by prion disease (main effect of disease: F = 107.98, df 1, 12, p < 0.0001) but is not significantly affected by poly I:C (F = 0.79, df 1, 12, p = 0.39).