Fig. 6

Overexpression of a constitutively active form of IRF3 leads to proinflammatory phenotype and induces expression of the AD risk genes. A GO analysis of the differentially upregulated genes in FACS-sorted myeloid cells from IRF3-2D,Cre_Tam mice compared to Cre_only show proinflammatory phenotypes and upregulation of pathways related to interferon-β, γ signaling, cell adhesion, and leukocyte proliferation. B Volcano plot showing differentially expressed genes in IRF3-2D,Cre_Tam mice compared to Cre_Tam. Note the upregulation of AD-associated genes. (n = 2 for Cre_Tam, n = 3 for IRF3-2D,Cre_Tam). C-D Representative images of APOE staining in the cortex. Quantification confirms that APOE levels are significantly upregulated in the microglia from IRF3-2D,Cre_Tam group. The scale bar is 21 μM. N = 6,8 per group. One-way Anova with Sidak’s multiple comparison test. **p < 0. 01. E Deconvolution analysis on myeloid cells from IRF3-2D,Cre_Tam mice shows significantly more ARM-like cell fraction compared to Cre_only fraction. Both IRF3-2D,Cre_Oil and IRF3-2D,Cre_Tam cells contain IRM- populations in response to IRF3-2D-mediated signaling. F-G Western blot image and quantification of cell lysates from primary WT microglia treated with Aβ oligomers (2.5 μM) for 24 h, show significant IRF3 phosphorylation. N = 8,9 each group. Student’s t-test with Welch’s correction. *p < 0.05