The SQSTM1 agonists enhance xenophagy-mediated host defense against pathogens in mice. (A) Mice were injected p.o. with 1 × 106
S. Typhimurium in PBS, followed by administration of SQSTM1 agonist (20 mg/kg) by i.p. once daily (n = 4 per group). Bacterial burdens in the liver (upper panel) and spleen (lower panel) were analyzed by CFU assay after 6 dpi. (B) Representative H&E staining images of liver from S. Typhimurium infection model injected i.p. with vehicle (Control) or 20 mg/kg YTK-2205. (C) Bacterial burdens in mouse lung tissues. Mice were infected i.n. with Mtb (5 × 104 CFU). After infection, mice were treated with vehicle, YTK-2205 (i.p. 10 mg/kg; n = 7 per group, left), or YT-6-2 (i.p. 20 mg/kg; n = 5 per group, right). (D) Representative H&E-stained images in lung tissue of mice treated as in c. Scale bars: 2000 µm and 100 µm. (left panel). Quantitative graph represents the average percentage of inflamed area of tissue section (right panel). (E and F) Mice (n = 4 per group) were infected i.n. with BCG (1 × 107 CFU), and treated with vehicle or YTK-2205 (i.p. 20 mg/kg) at 3–6 dpi. (E) Bacterial loads determined by CFU analysis. (F) H&E staining of the BCG-infected lung tissue and representative images are shown. Scale bars: 2000 µm and 100 µm (left panel). Quantitative graph represents the average percentage of inflamed area of tissue section (right panel). (G) Bacterial loads in mouse lung tissues. Mice (n = 4 per group) were infected i.n. with MDR-Mtb (5 × 103 CFU), and treated with vehicle or YT-6-2 (i.p. 20 mg/kg).