Fig. 6: Proteomic analysis revealing pathogen-specific host response patterns.

A Doughnut chart showing pathogen proportions in 156 IE patients with positive mNGS results. B Heatmap showing differential plasma profiling across the four pathogen infections. Pearson’s two-sided χ² test evaluated associations between pathogen types and 12 variables. C, D Bubble charts showing enriched pathways for the four pathogens in the plasma and vegetation proteomes. E PPIs depicting the top three significant molecular complex detection (MCODE) components of the Streptococcus group. F Scatter plot showing plasma proteins according to their correlation with neutrophil count in the Streptococcus group (x-axis) and abundance differences from other groups (y-axis). G Boxplot depicting the relative abundance of the vegetation protein MPO (log2) across Streptococcus (n = 75), C. burnetii (n = 18), S. aureus (n = 13), and CoNS (n = 9) groups. The central line represents the median, the box indicates the IQR, and whiskers extend to 1.5 × IQR, with outliers as individual points. H Overlap rate of detectable vegetation in each group. I Volcano plot showing vegetation DEPs between the two groups. J Venn diagram illustrating 26 vegetation proteins correlated with MPO (R > 0.5, p < 0.05) and upregulated in the Streptococcus & S. aureus group (FC > 1.5, p < 0.05). K, L Bubble chart and heatmap displaying the enriched pathways and the proteins included for the 26 proteins. M IF staining of MPO and citrullination of histone H3 (CitH3) in representative Streptococcus and C. burneti infections. Scale bar, 20 μm. Boxplot showing the proportion of CitH3-positive areas in the two groups (n = 5). Data are presented as mean ± SEM. The unpaired two-sided Student’s t test was used. N Summary of the harmful effects of excessive NET release in patients infected with Streptococcus & S. aureus. For figures (F, G, I, J), the unpaired two-sided Wilcoxon rank-sum test and Kruskal–Wallis test were used for differential analysis. For figures (F, J), the two-sided Spearman’s correlation was used, with p-values adjusted for FDR. Source data are provided as Source Data files.