Extended Data Fig. 10: AIM2 regulates Pyrin and ZBP1 expression in vivo, and AIM2 provides host protection against HSV1 and F. novicida.
From: AIM2 forms a complex with pyrin and ZBP1 to drive PANoptosis and host defence
a, b, Immunoblot analysis of pro- (P45) and activated (P20) caspase-1 (CASP1), pro- (P53) and activated (P30) gasdermin D (GSDMD), pro- (P55) and cleaved (P18) caspase-8 (CASP8), pro- (P35) and cleaved (P17/P19) caspase-3 (CASP3), pro- (P35) and cleaved (P20) caspase-7 (CASP7), phosphorylated MLKL (pMLKL), total MLKL (tMLKL), ZBP1, Pyrin and AIM2 in lung from uninfected animals (PBS) or wild type (WT) or Aim2−/− mice 3 days after HSV1 (a) or F. novicida (b) infection. Each lane indicates independent biological replicates. c, Viral quantification in WT, Aim2−/−, Mefv−/−, Zbp1−/− or Mefv−/−Zbp1−/− BMDMs at 16 h post-infection with HSV1. Data are mean ± s.e.m. ****P < 0.0001 (one-way ANOVA with Dunnett’s multiple comparisons test; n = 6 from 3 biologically independent samples). d, Bacterial quantification in WT, Aim2−/−, Mefv−/−, Zbp1−/− or Mefv−/−Zbp1−/− BMDMs after F. novicida infection. Data are mean ± s.e.m. *P < 0.05 and ****P < 0.0001 (one-way ANOVA with Dunnett’s multiple comparisons test; n = 3 from 3 biologically independent samples). e, In vivo bacterial quantification in lung, liver or spleen from WT or Aim2−/− mice 2 days after F. novicida infection (n = 5). Each symbol represents one mouse. Data are pooled from two independent experiments. Data are mean ± s.e.m. **P < 0.01 and ***P < 0.001 (two-tailed t-test). f, Survival of WT, Aim2−/−, Mefv−/− and Zbp1−/− mice infected subcutaneously with 5 × 105 CFU of F. novicida in 200 μl PBS. Survival data are pooled from three independent experiments. **P < 0.01; ****P < 0.0001 (log-rank (Mantel-Cox) test). Exact P values are presented in Supplementary Table 1. For gel source data, see Supplementary Figure 1.
