Extended Data Fig. 3: STING suppresses lactate production independent of its innate immune function.

a, WT, Sting1^−/− L929 cells and the reconstituted Sting1^−/− L929 cells were analysed by immunoblotting. b, Sting1^−/− L929 cells reconstituted with vector control, STING WT or the indicated mutants were stimulated with or without HT-DNA, and Isg56 or Cxcl10 mRNA was quantified at 6 h post-stimulation. c, immunoblotting analysis of STING-S366A reconstituted Sting1^−/− L929 cells stimulated with HT-DNA or infected with HSV-1 for the indicated amount of time. d, immunoblotting analysis of STING-R238A reconstituted Sting1^−/− L929 cells stimulated with HT-DNA or infected with HSV-1 for the indicated amount of time. e, Cgas^−/− L929 cells reconstituted with vector control or cGAS were stimulated with or without HT-DNA, and Isg56 and Cxcl10 mRNA was quantified at 6 h post-stimulation. f and g, Immunoblotting of the reconstituted Cgas^−/− L929 cells stimulated with HT-DNA (f) or infected with HSV-1 (g) for the indicated amount of time. h, L929 cells were transduced with control sgRNA or sgRNA targeting IRF3, and the stable cells were further transduced with control sgRNA or sg-STING to generate double knockout cells. WCLs were analysed by immunoblotting and lactate production was measured. i, Mouse lung fibroblasts (MLFs) isolated from WT or Ifnar1^−/− mice were stimulated with or without Interferon-β (IFNβ), and Cxcl10 or Isg56 mRNA was quantified by qPCR at 6 h post-stimulation. j and k, WT and Ifnar1^−/− MLF cells were transduced with control sgRNA or sg-STING. WCLs were analysed by immunoblotting (j) and lactate production was measured (k). Data are presented as means ± s.d. of n = 3 independent biological replicates for b, h, i, k, and n = 4 independent biological replicates for e. P-values were calculated by two-tailed Student’s t-test. Data are representative of three independent experiments. Uncropped gel images and numerical data are available in source data.

Source data