Disruption of neutrophil GSDMD does not protect the host from sepsis. (A) Polymicrobial sepsis was induced in WT and Gsdmd KO mice (N = 10/group) via CLP, and survival was monitored for up to 10 days. (B) Survival of neutrophil-specific–conditional KO mice and their counterparts during sepsis. Gsdmd^flox/floxMRP8-Cre⁺ (N = 13) and WT counterpart mice (N = 10) were subjected to polymicrobial sepsis using CLP. The survival was monitored. Data were analyzed using the log-rank (Mantel-Cox) test. (C-H) Sepsis was induced in Gsdmd^f+/f+MRP8-Cre⁺ and littermate WT control Gsdmd^f+/f+MRP8-Cre^- mice via CLP. Twelve hours after CLP, mice were euthanized to collect PF and serum. (C) Neutrophil recruitment to the peritoneal cavity as measured by flow cytometry. (D) Cytokines (TNF-α, IL-1β, IL-10, and IL-6) in cell-free PF. (E) Cytokines in serum. (F) Lactate dehydrogenase levels in PF. (G) The bacterial burden in the PF was quantified. (H) NETs production in peripheral blood and peritoneal cavity. Data are presented as mean ± SEM. The log-rank (Mantel-Cox) test was used to analyze survival differences between groups. In other graphs, t-test was used to compare the means. ∗P < .05; ∗∗P < .01. CFU, colony forming units; LDH, lactate dehydrogenase; PC, peritoneal cavity; PF, peritoneal lavage fluid; SEM, standard error of the mean.