Fig. 3: SARS-CoV-2 infection of human macrophages activates inflammasomes and pyroptosis.

a, CXCL10⁺ or TNF⁺ human macrophages (MΦ). Representative of n = 6 mice over 3 experiments. b, CXCL10⁺ lung macrophage frequencies after monoclonal antibody or remdesivir therapy. n = 9 (control infected), n = 4 (monoclonal antibodies) and n = 6 (RDV) mice over 2 experiments. Mean values are shown with data points. c, Serum CXCL10 levels after monoclonal antibody or remdesivir therapy. Mean values are shown with data points. n = 4 (uninfected; monoclonal antibodies); n = 7 (control infected) and n = 3 (RDV) mice examined over 2 experiments. d, Correlation (Pearson and Spearman) of each gene with CXCL10, TNF or TLR7 in human lung monocytes and macrophages. k-means clustering. P values were calculated based on a t-distribution with length(x) − 2 d.f. or algorithm AS 89 with exact = TRUE; two-tailed. e, Representative plots and AM frequencies within mNG⁺ or mNG⁻ macrophages. n = 8 mice examined over 4 experiments. f, ASC speck visualization/quantification and colocalization with active caspase-1 (FLICA) in mNG⁺ or mNG⁻ human immune cells from MISTRG6-hACE2 mouse lungs. Cells were sorted as shown in Extended Data Fig. 6j. n = 1,000 cells were analysed per condition. ASC⁺ specks: n = 3 (A, 4 d.p.i.), n = 5 (B–D, 4 d.p.i.) and n = 3 mice (14 d.p.i.); FLICA: n = 3 mice examined over at least 2 experiments. Data are mean ± s.d. with data points. BF, bright field. NS, not significant. g, ASC speck visualization/quantification and colocalization with NLRP3 oligomerization in sorted mNG⁺ or mNG⁻ human lung immune cells. n = 1,000 cells were analysed per condition. n = 3 mice over 2 experiments. Data are mean ± s.d. with data points. For f and g, scale bars 7 μm. BF, bright field. h, Serum IL-18, IL-1RA and GSDMD levels. IL-18: n = 4 mice were examined over 2 experiments; IL-1RA: n = 5 (uninfected), n = 7 (4 d.p.i.) and n = 4 (14 d.p.i.) mice were examined over 3 experiments; GSDMD: n = 4 (uninfected; 4 d.p.i.) and n = 5 (14 d.p.i.) mice over 3 experiments. Mean values are shown with data points. P < 0.0001 represents P = 3.32 × 10⁻⁷. i, Serum IL-18 and IL-1RA levels in mice treated with CD16-blocking or CD16-depleting antibodies or remdesivir. IL-18: n = 4 (uninfected; CD16 blocking; CD16 depleting), n = 7 (control infected) and n = 3 (RDV); IL-1RA: n = 5 (uninfected), n = 7 (control infected), n = 6 (RDV), n = 4 (CD16 blocking; CD16 depleting) mice were examined over at least 2 experiments. Mean values are shown with data points. P < 0.0001; uninfected, P = 3.28 × 10⁻⁵; CD16 depletion, P = 7.92 × 10⁻⁷. For b, c and f–i, statistical analysis was performed using unpaired two-tailed t-tests.

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