Extended Data Fig. 4: Pyrin and ZBP1 are required for AIM2-mediated cell death following HSV1 infection, but not in response to poly(dA:dT).
From: AIM2 forms a complex with pyrin and ZBP1 to drive PANoptosis and host defence
a, b, Quantification of cell death in wild type (WT), Aim2−/−, Mefv−/−, Zbp1−/− or Mefv−/−Zbp1−/− bone marrow-derived macrophages (BMDMs) over time during HSV1 (a) and F. novicida (b) infections. Data are mean ± s.e.m. *P < 0.05; ***P < 0.001; ****P < 0.0001 (one-way ANOVA with Dunnett’s multiple comparisons test; n = 4). Data are representative of at least three independent experiments. c, Cell death in THP-1 macrophages treated with control siRNA (Control) or siRNA targeted to AIM2 (AIM2 KD), MEFV (MEFV KD) and/or ZBP1 (ZBP1 KD) after HSV1 infection. Red indicates dead cells. Images are representative of at least three independent experiments. Scale bar, 50 μm. d, Quantification of the cell death from (c). Data are mean ± s.e.m. ****P < 0.0001 (one-way ANOVA with Dunnett’s multiple comparisons test; n = 4). Data are representative of at least three independent experiments. e, Immunoblot analysis of caspase-1 (CASP1) activation and AIM2, Pyrin and ZBP1 expression in the indicated THP-1 cells. Data are representative of two independent experiments. f, Cell death in WT, Aim2−/−, Mefv−/−, Zbp1−/− or Mefv−/−Zbp1−/− BMDMs after poly(dA:dT) transfection. Red indicates dead cells. Images are representative of at least three independent experiments. Scale bar, 50 μm. g, Quantification of the cell death from (f). Data are mean ± s.e.m. ns, not significant; ****P < 0.0001 (one-way ANOVA with Dunnett’s multiple comparisons test; n = 9 from 3 biologically independent samples). Exact P values are presented in Supplementary Table 1. h, Immunoblot analysis of CASP1 in the indicated BMDMs after poly(dA:dT) transfection. Data are representative of at least three independent experiments. For gel source data, see Supplementary Figure 1.
