Extended Data Fig. 8: dNTP availability controls LPS-induced mtDNA synthesis and NLRP3 inflammasome activation.

a, Relative total mtDNA amounts in shCtrl and shNme4 BMDMs before and after LPS priming. Data are mean ± s.d. (n = 3 biological replicates). b, Amounts of 8-OH-dG in mtDNA isolated from the mitochondrial fraction of LPS-primed shCtrl and shNme4 BMDMs that were stimulated with various NLRP3 activators. Data are mean ± s.d. (n = 3 biological replicates). c, Amounts of 8-OH-dG in cytosolic mtDNA from LPS-primed shCtrl and shNme4 BMDMs that were stimulated with various NLRP3 activators. Data are mean ± s.d. (n = 3 biological replicates). d, e, Amounts of IL-1β (d) and TNF (e) in supernatants of LPS-primed shCtrl and shNme4 BMDMs that were stimulated with various inflammasome activators. Data are mean ± s.d. (n = 3 biological replicates). f, Immunoblot analysis of SAMHD1 and Polγ in wild-type and Trif^−/− BMDMs that were stimulated with LPS for different durations as indicated. Results are typical of three independent experiments. g, Relative total mtDNA amounts in wild-type and Samhd1^−/− BMDMs before and after LPS stimulation. Data are mean ± s.d. (n = 3 biological replicates). h, i, Amounts of IL-1β (h) and TNF (i) in the culture supernatants of LPS-primed wild-type and Samhd1^−/− BMDMs that were stimulated with inflammasome activators as indicated. Data are mean ± s.d. (n = 3 biological replicates). j, Amounts of NLRP3 activator-induced IL-1β in culture supernatants of LPS-primed wild-type and Samhd1^−/− BMDMs with or without Polg expression. Data are mean ± s.d. (n = 3 biological replicates). *P < 0.05; **P < 0.01; ***P < 0.001; two-sided unpaired t-test.

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