Fig. 1: Phage therapy in the macrophage depleted host.

A Flow cytometry analysis of bronco alveolar lavages (BAL) from mice that were given 96 h before clodronate liposomes (depleted) or empty liposomes (control) by intra-tracheal instillation (n = 3-4 each). Cell debris and doublets were first excluded based on CD45 staining. Among the CD45+ population Ly6G+ was used to gate PMN, in the Ly6G- population, the CD11b- correspond to dendritic cells (DC) and alveoli macrophage (AM). The DCs were gated as F4/80- and CD11c+ low while the AM as F4/80+ and CD11c+ high (p value from Mann-Whitney U test two tailed, are indicated). B Survival of acute respiratory infection caused by P. aeruginosa (5 × 10⁶ CFU of strain PAKlumi) of AM-depleted mice (clodronate, n = 8) and control mice (n = 5) was significantly different (p = 0.0015 Mantel-Cox log rank test) in absence of phage treatment (full lines). With phage PAK_P1 (5 × 10⁷ PFU) administered intranasally at 2 h p.i. (dashed lines) in AM-depleted (n = 5) and control (EL) (n = 6) mice, phage treatment significantly improved their survival (p = 0.0058 and 0.0015, Mantel-Cox log rank test, for AM-depleted and control mice, respectively). Data were assembled from 5 independent experiments. C The colonization kinetics of the bioluminescent strain PAKlumi in the lungs is plotted as mean radiance (p/s/cm²/sr) over time with error bars representing SD. Groups of mice were infected and treated as in panel (B) with control (n = 6), AM-depleted (n = 8), phage-treated control (n = 9) and phage treated AM-depleted (n = 13). Statistical analysis (two-tailed Mann–Whitney U test) is indicated for the time point 22 h p.i. LOQ, limit of quantification. LOD, limit of detection. Data were assembled from 6 independent experiments. D Bacterial counts (CFUs in log scale) from lung homogenates taken from mice (same animals as in panel C) 22 h post infection. LOD limit of detection (p values from two-tailed Mann–Whitney U test are displayed). Data were assembled from 5 independent experiments.