Fig. 1.

Increased gene copy number of DEFA1/DEFA3 aggravates sepsis development. (A) Survival over time after performance of CLP in WT mice (n = 25), mice with a LCN of DEFA1/DEFA3 (n = 13), and mice with a HCN of DEFA1/DEFA3 (n = 12). Sham-operated mice were included as controls (n = 10 for each group). **P = 0.002, ***P < 0.001, log-rank test. (B) Quantification of the lung injury score based on H&E-stained lung sections of WT mice, mice with LCN of DEFA1/DEFA3, and mice with HCN of DEFA1/DEFA3 at 72 h after CLP or sham operation. **P = 0.003, ***P < 0.001, two-way ANOVA with Bonferroni posttests. (C) Quantification of the liver injury score based on H&E-stained liver sections of WT mice, mice with LCN of DEFA1/DEFA3, and mice with HCN of DEFA1/DEFA3 at 72 h after CLP or sham operation. ***P < 0.001, two-way ANOVA with Bonferroni posttests. (D) Quantification of the kidney injury score based on H&E-stained kidney sections of WT mice, mice with LCN of DEFA1/DEFA3, and mice with HCN of DEFA1/DEFA3 at 72 h after CLP or sham operation. **P = 0.002, ***P < 0.001, two-way ANOVA with Bonferroni posttests. (E) Survival over time of lethally irradiated WT mice that were reconstituted with BM from WT mice (n = 12), mice with LCN of DEFA1/DEFA3 (n = 13), and mice with HCN of DEFA1/DEFA3 (n = 12) and that were subsequently subjected to CLP. *P = 0.016, **P = 0.006, log-rank test. (F) Survival over time after intraperitoneal infection of WT mice (n = 18), mice with LCN of DEFA1/DEFA3 (n = 17), and mice with HCN of DEFA1/DEFA3 (n = 18) with E. coli (4 × 10⁶ colony forming units per mouse) prepared in 200 μL of PBS. Mice intraperitoneally injected with 200 μL of PBS were included as controls (n = 10 for each group). **P = 0.004 between WT mice and mice with HCN of DEFA1/DEFA3, **P = 0.008 between mice with LCN of DEFA1/DEFA3 and mice with HCN of DEFA1/DEFA3, log-rank test. In B–D, data are presented as dot plots with horizontal bars representing means ± SEM; n = 6 for each CLP group, and n = 5 for each sham group.