Fig. 1: Impairment of IFN-I pathway in blood monocytes 1 week after LPS-induced systemic inflammation.

a, Schematic representation of the study and sample acquisition in healthy volunteers (n = 11). Seven volunteers were intravenously (i.v.) injected with LPS (2 ng kg⁻¹) at baseline (BL, d0) and d7. Four volunteers were intravenously injected with placebo (0.9% NaCl) at BL. Peripheral blood was collected at BL, 4 h, 8 h, 24 h, d7 and d7 + 4 h. b, Box plots of absolute abundance of CD14⁺CD16⁻ cMonos, CD14⁺CD16⁺ iMonos and CD14⁻CD16⁺ ncMonos in blood of LPS-challenged volunteers (n = 7) at BL, 4 h and d7. c, Principal component analysis of blood CD14⁺ monocyte transcriptomes from LPS-challenged volunteers (n = 3) at BL, 4 h, 8 h, 24 h, d7 and d7 + 4 h. d, Heatmap representation of DEGs at 4 h, 8 h, 24 h, d7 and d7 + 4 h compared with BL as in c. e, GO term analysis of DEGs at 4 h, 8 h, 24 h, d7 and d7 + 4 h compared with BL as in c. f, Bar plots of TNF and IFNγ production in CD3⁺ T cells isolated from the blood of healthy donors (n = 9), activated with CD3 and CD28 antibody-coupled beads and co-cultured with cMonos obtained from LPS-challenged volunteers (n = 6) at BL and 4 h at 1:2 ratio. g, Bar plots of percentage of proliferating CD3- and CD28-activated CD3⁺ T cells isolated from the blood of healthy donors (n = 9), and co-cultured with cMonos obtained from LPS-challenged volunteers (n = 6) at BL and 4 h at 1:2 ratio as in f. h, GSEA of gene expression profiles at 4 h, 8 h, 24 h, d7 and d7 + 4 h compared with BL as in c. i, DEGs in blood CD14⁺ monocytes from LPS-challenged volunteers (n = 3) in response to both LPS challenges (first: 4 h versus BL; second: 7 d + 4 h versus 7 d) clustered into three groups: responsive (FC < 2), semi-suppressed (2 < FC < 3) and suppressed (FC > 3). j, GO term analysis of responsive, semi-suppressed and suppressed genes in CD14⁺ monocytes from LPS-challenged volunteers (n = 3) as in j. k, Percentage of responsive (FC < 2), semi-suppressed (2 < FC < 3) and suppressed (FC > 3) DEGs in blood CD14⁺ monocytes from LPS-challenged volunteers (n = 3) obtained at 4 h, 8 h, 24 h and d7 that were ex vivo stimulated with LPS (10 ng ml⁻¹) versus CD14⁺ LPS-stimulated monocytes obtained at BL. l, Heatmap representation of average expression of DEGs in CD14⁺ restimulated monocytes from LPS-challenged volunteers (n = 3) obtained at 4 h, 8 h, 24 h and d7 based on fold-change relative to BL (n = 3) as in k. Genes were clustered (C1–C6) based on their behavior across the different time points. m, GO term analysis of genes in clusters C1–C6 defined as in l. The box plots in b show the median, first and third quartiles and the whiskers 1.5× the interquartile range (IQR). The bar plots in f and g are presented as mean values ± s.e.m. The P values were calculated using two-sided, paired Wilcoxon’s signed-rank tests.