Figure 5

Enhanced S. Typhimurium susceptibility in Asc^−/−and Nlrp3^−/−mice in the colitis model. WT (white), Asc^−/− (grey) and Nlrp3^−/− (black) mice were pretreated with streptomycin and orally infected with S. Typhimurium (10⁶; colitis model). Compared to WT mice, Asc^−/− mice show completely abolished IL-18 levels in plasma measured 4 days post infection, while Nlrp3^−/− mice have similar IL-18 concentrations (A). In the bar chart, the mean and SEM is shown, dashed lines represent the detection limit of the ELISA. Bacterial titers of S. Typhimurium were determined in the mesenteric lymph nodes (MLN) (B), liver (C) and blood (D) in both the Asc^−/− and Nlrp3^−/− mice 4 days post infection. Total liver- (E) and spleen- (F) pathology scores were determined 4 days post infection according to the scoring system as described in Methods. The median (straight lines) and the detection limit (dashed lines) are shown. Aspartate transaminase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH) were measured in blood plasma from WT, Asc^−/− and Nlrp3^−/−(G-I) mice after oral infection with S. Typhimurium (10⁶). UI, uninfected controls (striped). In the bar chart, the mean and SEM is shown. Graphs depict 8–12 mice per genotype and per time-point. Representative slides of liver haemotoxylin and eosin (HE) staining of WT (J), Asc^−/− (K) and Nlrp3^−/− (L) mice 4 days post infection. All groups showed severe liver inflammation with thrombus formation (#). Arrowheads indicate inflammatory cells. Original magnification. × 10. Statistical significance was determined using the unpaired Mann- Whitney U test. *, p < 0.05, **, p < 0.01.