Figure 7: Conditional knockout of PKM2 in myeloid cells protects septic mice.

(a) Western blot analysis of expression of indicated proteins in BMDMs or lung isolated from myeloid cell-specific PKM2-knockout mice (PKM2^−/−) and control WT mice (PKM2^+/+). (b) Indicated mice (n=10 mice per group) were pre-injected with LPS (2 mg kg⁻¹, intraperitoneally) for 3 h and then challenged with NLRP3 activator ATP (200 mg kg⁻¹, intraperitoneally) or AIM2 activator nucleosome (20 mg kg⁻¹, intraperitoneally). Injection with LPS (2 mg kg⁻¹, intraperitoneally) alone in these mice was used as a control (n=10 mice per group). The Kaplan–Meyer method was used to compare differences in survival rates between groups (*P<0.05). (c,d) In parallel experiments, serum levels of IL-1β and HMGB1 at indicated time points were measured (n=3 animals per group, *P<0.05, ANOVA LSD test). (e) Schematic depicting PKM2-mediated glycolysis promoting NLRP3 and AIM2 inflammasome activation and proinflammatory cytokine (for example, IL-1β, IL-18 and HMGB1) release by modulating EIF2AK2 phosphorylation. All quantification data expressed as means±s.e.m of three independent experiments. Western blot data are representative of two independent experiments.