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Fig. 3 | Acta Neuropathologica Communications

Fig. 3

From: Lipid-specific IgMs induce antiviral responses in the CNS: implications for progressive multifocal leukoencephalopathy in multiple sclerosis

Fig. 3

O4 response is mediated by Ifnar1 and microglia-derived interferon-β in a cGAS-STING-TBK1-IKKε dependent manner. a-h RT-qPCR analysis of ISG expression in a-d WT and Ifnar1−/− mouse cultures treated 24 h with A4CD or O4 and e-h rat cultures treated 24 h with A4CD or O4 in combination with rabbit IgG or anti-rat IFN-β neutralising antibody. Data presented as mean fold change compared to untreated control ± SEM, analysed by two-way ANOVA, significant interaction denoted *p < 0.05, **p < 0.01, ***p < 0.001 and ****p < 0.0001. WT (n = 2), Ifnar1−/− (n = 4), IFN-β neutralisation experiment (n = 3 all conditions). i-m Rat cultures treated 10 days with DMSO or PLX3397 followed by 6 h treatment with A4CD or O4. i, j Iba1 staining. k, l Iba1+ and DAPI+ cells. Data presented as mean ± SEM, significant difference determined by paired two-tailed t-test, *p < 0.05. m RT-qPCR analysis of Ifnb1 expression. Data presented as mean fold change compared to untreated control ± SEM, analysed by two-way ANOVA, significant interaction denoted *p < 0.05, n = 3 for all conditions. n Ifnb1 expression in rat cultures treated 6 h with O4 alone or in combination with vehicle or inhibitor of interest (10 μM). Data presented as mean fold change compared to untreated control ± SEM, analysed by one-way ANOVA with Tukey’s post hoc test. Significant difference compared to O4 alone denoted as *p < 0.05. O4 alone (n = 6), DMSO (n = 6), ST2825 (n = 3), RU.521 (n = 2), C-176 (n = 5) and BX795 (n = 3)

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