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. Author manuscript; available in PMC: 2018 Jan 4.
Published in final edited form as: Science. 2017 Aug 4;357(6350):498–502. doi: 10.1126/science.aam5336

Fig. 3. DAT protects from influenza via type I IFN signaling.

Fig. 3

(A) Kaplan-Meier survival analysis of groups of mice treated without antibiotics (left) or with a cocktail of broad-spectrum antibiotics (right, VNAM) and then treated with or without DAT before infection (n = 30 mice per group from two experiments, inclusive of all groups but plotted separately for clarity). (B) Kaplan-Meier survival analysis of Ifnar−/− mice treated with or without DAT and infected with influenza (n = 18 to 21 mice per group from two experiments). (C) Infectious viral load determined by plaque assay at day 5 postinfection for groups of mice from (A) (n = 10 mice per group from two experiments). (D) Matrix viral RNA expression determined by qRT-PCR from lung homogenates of mice treated with or without DAT as in (C). (E and F) Representative images of lung cross sections from mice treated with or without DAT at 5 days postinfection. Boxed areas are magnified immediately below. (E) H&E stained sections. Scale bar, 50 µm. (F) Sections stained for cleaved caspase 3 by immunohistochemistry. Scale bar, 20 µm. (G) Percentage of airways positive for at least one cleaved caspase–positive cell within an airway cross section [n = 10 mice per group from two experiments for (E) to (G)]. (H) Time course of quercetin degradation after incubation with control, mouse cecal contents, or single bacterial species (n = 6 replicates per group from two experiments). (I) Kaplan-Meier survival analysis of VNAM-pretreated mice gavaged twice with PBS, cecal contents, or single bacterial species and then infected with influenza (n = 20 mice per group from two experiments for PBS, cecal contents, C. orbiscindens gavage or 10 mice per group for C. leptum or E. fecalis gavage). (J) Stool DAT levels measured by mass spectroscopy at time of infection in mice from (I) (n = 10 per group). Statistical significance per group is compared with PBS-gavaged group. Means ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001; and ns, not statistically significant. Mantel-Cox test with or without Bonferroni-corrected threshold used in (A), (B), and (I). Mann-Whitney test used in (C), (D), and (G). ANOVA used in (H) (F = 50.8) and (J) (F = 14.5) with Dunnett's multiple-comparisons test.