Fig. 1.

Therapeutic effects of flagellin in experimental sepsis. a Various doses of flagellin (0, 2, 5, 10 μg) were injected intraperitoneally into cecal ligation and puncture (CLP)–induced septic mice at 2 h after lethal CLP using 21-gauge needle, and survival was monitored (n = 16 per group). Comparison between groups was done by Kaplan–Meier analysis followed by log-rank tests. ***p < 0.001 when compared with mice treated with phosphate-buffered saline (PBS) control. b CLP mice were given intraperitoneally 5 μg of flagellin at 2, 4, 6, and 8 h after CLP, and survival was monitored (n = 16 per group). Comparison between groups was done by Kaplan–Meier analysis followed by log-rank tests.*p < 0.05, **p < 0.01, and ***p < 0.001 when compared with mice treated with PBS control. c Clinical appearance of flagellin-treated (5 μg) and control mice at 24 h after CLP. d Bacterial counts in peritoneal lavage fluid (PLF), spleens, or blood from mice (n = 5 per group) treated with or without flagellin (5 μg) at 24 h after CLP. Horizontal bars represent median values, and dots represent individual mice. ***p < 0.001when compared between groups (denoted by horizontal bracket; Mann–Whitney U test). e CLP mice (n = 20 per group) were given intraperitoneally 50 μg of anti-TLR5-neutralizing monoclonal antibodies at 2 h before CLP, followed by flagellin (5 μg) treatment at 2 h after CLP, and survival was then monitored. Comparison between groups was done by Kaplan–Meier analysis followed by log-rank tests. ***p < 0.001 when compared with mice treated with isotypical IgG. f Clinical appearance of flagellin-treated (5 μg) mice with or without TLR5 neutralization at 24 h after CLP. g Bacterial counts in PLF, spleens, or blood from flagellin-treated (5 μg) mice (n = 5 per group) with or without TLR5 blockade using anti-TLR5 antibodies (50 μg) or TLR5 Fc Chimera (50 μg) at 24 h after CLP. *p < 0.05, **p < 0.01, and ***p < 0.001 when compared with control mice