Fig. 3: In vivo antimicrobial activity of the PPP1CB-derived peptide in models of pneumonia, bacteraemia and sepsis.
From: Cell-autonomous innate immunity by proteasome-derived defence peptides
a, Pneumonia model. i.n., intranasal. b, Box plots of CFU count of P. aeruginosa (log10) per lung in mice treated with PBS, PPP1CB (5 mg kg–1 i.v.) or tobramycin (50 mg kg–1 i.p.). Data are mean ± s.d. (n = 8). One-way ANOVA, ****P < 0.0001. c, Representative haematoxylin and eosin (H&E)-stained and Gram-stained lung tissue sections from uninfected mice or mice infected with P. aeruginosa (Pa) treated with vehicle (PBS) or PPP1CB peptide (5 mg kg–1 i.v.). Scale bars, 50 µm (uninfected (H&E), Pa PPP1CB (H&E) and Pa PBS (H&E)) and 20 µm (Pa PBS (100×, Gram)). Red arrows indicate bacterial staining. d, Bar plot showing mean ± s.e.m. of tissue injury in the pneumonia model. One-way ANOVA, **P < 0.01, ***P < 0.001. e, Neutrophil infiltration analysis in lung tissue graded on the basis of severity: 1, minimal (<1%); 2, slight (1–25%); 3, moderate (26–50%); 4, moderate–severe (51–75%); 5, severe–high (76–100%). Data are mean ± s.e.m., one-way ANOVA, **P < 0.01. f, bacteraemia model. g, Box plots of CFU count of P. aeruginosa (log10) per spleen in mice treated with PBS, PPP1CB (10 mg kg–1 i.v.) or tobramycin (50 mg kg–1 i.p.). Data are mean ± s.d. (n = 8). One-way ANOVA, ****P < 0.0001. h, Representative H&E-stained and Gram-stained tissue sections from spleen uninfected or treated with PBS or PPP1CB peptide (10 mg kg–1 i.v.). Scale bars, 50 µm (H&E stained) and 20 µm (Gram stained). i–m, Bar plots representing the degree of lesions in different organs (spleen (i), heart (j), kidney (k), liver (l), lung (m)) in the bacteraemia model. Data are mean ± s.e.m. One-way ANOVA, *P = 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. n, Kaplan–Meier survival curve showing survival rates of mice treated with PBS, PPP1CB or tobramycin (10 mg kg–1 retro-orbitally (r.o.) for both treatments) over six days after P. aeruginosa infection. Log-rank test, ****P < 0.0001, followed by pairwise comparisons using log-rank tests. NS, P > 0.05 (n = 15). Schematics in panels a and f created with BioRender.com (https://BioRender.com/x10a923).
