Figure 2.
SIRT3 is required for controlling pathological inflammation and neutrophil infiltration during mycobacterial infection. (a-e) Sirt3+/+ and sirt3−/- (n = 8 each group) mice were infected intranasally with Mtb (3 × 104 CFU), and monitored at 7dpi. (a) Quantitative real-time PCR of lung Tnf and Il6 mRNA expression; (b and c) TNF immunoreactivity in ADGRE1/F4/80-positive cells in lung tissues (Representative images for b, Scale bars: 50 µm; quantitative analysis for c). (d and e) CXCL5 immunoreactivity in lung tissues (Representative images for d, Scale bars: 50 µm; quantitative analysis for e). (f and g) Sirt3+/+ and sirt3−/- BMDMs were infected with Mtb (MOI = 10) at the indicated times, and then subjected to quantitative real-time PCR (f) and cytokine ELISA (g) analysis. (h) Bacterial burden of Mtb-infected Sirt3+/+ and sirt3−/- mice (n = 5 each group) by depletion of neutrophils. The neutrophil-specific anti-LY6G Ab (clone 1A8) or the isotype control (clone 2A3) was treated 7 days after Mtb infection. *P < 0.05, **P < 0.01, ***P < 0.001 compared with Sirt3+/+ conditions (f and g). Two-way ANOVA (a, c, e, f, and g) or one-way ANOVA with Dunn’s multiple comparison test (h). Data are representative of three independent experiments (b,d and h left), values represent means (± SEM) from three or four independent experiments performed in triplicate (a,c, and e-g), and represent combined results of three independent experiments (h right).