Gut Tregs control intestinal immune pathology in SSP hosts. (A) Frequency and numbers of Tregs isolated from the colonic lamina propria (cLP; circle) of F1-uninfected and F1-SSP mice at 28 dpi (n = 5–10). (B) Representative FACS plots and frequency of Ki-67+ Tregs isolated from the colonic lamina propria of F1-uninfected and F1-SSP mice at 28 dpi (n = 5–10). (C) Representative FACS plot of tetramer+ (2W:I-Ab) Foxp3+ CD4+ T cells isolated from the colonic lamina propria of F1-SSP mice at 28 dpi. (D) Schematic representation of the experimental design. F1-Foxp3DTR mice (n = 10) were infected or not with Salmonella Typhimurium SL1344 (108 CFUs; STm), treated with streptomycin to induce SSP at 14 dpi, and injected (i.p.) or not with DT to deplete Tregs (ΔTreg) at 21, 22, and 25 dpi, as indicated. (E) Percentage of body weight variation and survival curve of ΔTreg (open black circle), ΔTreg superspreader (ΔTreg SSP; orange circle), and F1-SSP (green circle) mice (n = 10–15). (F)STm CFUs measured in the feces of F1-SSP and ΔTreg SSP at 28 dpi (n = 10–15). (G) Representative images (left) and H&E staining (right) of colonic tissues of ΔTreg, F1-SSP, and ΔTreg SSP at 28 dpi, as indicated. Magnification of H&E sections: upper panels = 1.25×; lower panels = 20×. Scale bars: upper panels = 1.0 mm; lower panels = 50 μm. Inflammation in the lamina propria (black asterisks) and in the submucosa (red asterisk); goblet cells (black arrows); edema in the submucosa (red asterisks); areas of ulceration (red arrowheads). (H) Pathology scores assigned to colonic tissue sections of ΔTreg, F1-SSP, and ΔTreg SSP at 28 dpi (n = 4–8). (I) FITC-dextran detected in the serum of ΔTreg, F1-SSP, and ΔTreg SSP mice at 28 dpi (n = 5–10). Results are representative of at least two independent experiments and presented as means ± SEM. Normality was assessed by the D’Agostino–Pearson test. The Mann–Whitney U test (A, B, and F) was used to compare two groups. One-way ANOVA (H and I) followed by post hoc Tukey’s test or Two-way ANOVA (E) followed by post hoc Sidak’s test was performed for multiple comparisons (****P < 0.0001; ***P < 0.001; **P < 0.01; *P < 0.05; ns = not significant). See also Fig. S2 and Table S1.
Figure 2.

Gut Tregs control intestinal immune pathology in SSP hosts. (A) Frequency and numbers of Tregs isolated from the colonic lamina propria (cLP; circle) of F1-uninfected and F1-SSP mice at 28 dpi (n = 5–10). (B) Representative FACS plots and frequency of Ki-67+ Tregs isolated from the colonic lamina propria of F1-uninfected and F1-SSP mice at 28 dpi (n = 5–10). (C) Representative FACS plot of tetramer+ (2W:I-Ab) Foxp3+ CD4+ T cells isolated from the colonic lamina propria of F1-SSP mice at 28 dpi. (D) Schematic representation of the experimental design. F1-Foxp3DTR mice (n = 10) were infected or not with Salmonella Typhimurium SL1344 (108 CFUs; STm), treated with streptomycin to induce SSP at 14 dpi, and injected (i.p.) or not with DT to deplete Tregs (ΔTreg) at 21, 22, and 25 dpi, as indicated. (E) Percentage of body weight variation and survival curve of ΔTreg (open black circle), ΔTreg superspreader (ΔTreg SSP; orange circle), and F1-SSP (green circle) mice (n = 10–15). (F)STm CFUs measured in the feces of F1-SSP and ΔTreg SSP at 28 dpi (n = 10–15). (G) Representative images (left) and H&E staining (right) of colonic tissues of ΔTreg, F1-SSP, and ΔTreg SSP at 28 dpi, as indicated. Magnification of H&E sections: upper panels = 1.25×; lower panels = 20×. Scale bars: upper panels = 1.0 mm; lower panels = 50 μm. Inflammation in the lamina propria (black asterisks) and in the submucosa (red asterisk); goblet cells (black arrows); edema in the submucosa (red asterisks); areas of ulceration (red arrowheads). (H) Pathology scores assigned to colonic tissue sections of ΔTreg, F1-SSP, and ΔTreg SSP at 28 dpi (n = 4–8). (I) FITC-dextran detected in the serum of ΔTreg, F1-SSP, and ΔTreg SSP mice at 28 dpi (n = 5–10). Results are representative of at least two independent experiments and presented as means ± SEM. Normality was assessed by the D’Agostino–Pearson test. The Mann–Whitney U test (A, B, and F) was used to compare two groups. One-way ANOVA (H and I) followed by post hoc Tukey’s test or Two-way ANOVA (E) followed by post hoc Sidak’s test was performed for multiple comparisons (****P < 0.0001; ***P < 0.001; **P < 0.01; *P < 0.05; ns = not significant). See also Fig. S2 and Table S1.

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