Blocking NLRP6-mediated necroptosis in WT mice improves host defense during <i>S</i>. <i>aureus</i> infection.

WT and KO mice (N = 6-8/group) were treated with either GW806742X (100 μl of 100 μM solution, i.p., 12 hours prior to infection) or an equivalent amount of DMSO prior to infection with a sublethal dose of S. aureus. Mice were euthanized 24 hours post infection to collect lungs and BALF. (A) Total protein and (B) LDH release in the BALF, bacterial burden in (C) lungs and (D) BALF were measured. (E) IL-1β, (F) TNF-α, and (G) MCP-1 in the cell-free BALF were measured. (H) Total leukocytes, (I) neutrophils, and (J) macrophages in the BALF was determined. (K) WT mice (N = 15/group) were treated with either Nec-1s (300 μg/mouse) or an equivalent amount of DMSO, 18 hours before and at the time of infection with S. aureus (2X108 CFU/mouse). Survival was monitored for up to 80 hours. Each figure is representative of three independent experiments. GW806742X: MLKL inhibitor, Nec-1s: Necrostatin-1s. *, p<0.05, **, p<0.01, and *** p<0.001.