Extended Data Figure 8: Interferon can enter via an intact blood–brain barrier and is sufficient to trigger engulfment of neuronal material by microglia.

a, Gating for tau-GFP⁺ microglia for engulfment analysis based on tau-GFP⁻ control mice (gate set to <0.5% in tau-GFP⁻ mice). b, The tau-GFP mean fluorescence intensity (MFI) for microglia was significantly higher in the frontal cortex of 564Igi relative to wild-type mice. n = 3 mice per group, ****P < 0.0001, two-way ANOVA with Sidak’s test. c, Intravenous injection of 10 kDa FITC–dextran tracer revealed no leakage of the dye from blood vessels (CD31⁺) in 564Igi mice up to 24 weeks of age. d, Staining for IgG revealed no increase in IgG deposition within the CNS in 564Igi mice compared to C57BL/6 controls, whereas MRL-lpr did show a notable increase. e, Colocalization of FITC–dextran with CD31 (blood vessels) showed that similar colocalization was observed in 564Igi mice and controls, indicating that similar amounts of dye were contained within vessels in both groups. n = 3 mice per group, P > 0.05, unpaired t-test. f, Quantification of MFI for IgG revealed no significant changes between 564Igi and C57BL/6 controls. MRL-lpr mice showed a significant increase compared to MRL-mpj controls. n = 3 mice per group, ****P < 0.0001, one-way ANOVA with Tukey’s test. g, h, Flow cytometry analysis of tau-GFP mice injected with IFNα (g) or IFNβ (h) demonstrated significant increases in tau-GFP⁺ frequencies compared to vehicle. n = 3 mice per group, *P < 0.05, **P < 0.01, unpaired t-test. Data are mean ± s.e.m. (b, e–h).