Fig. 1: Inflammatory monocytes trigger TNFα-centered cytokine storm in HFRS patients.

a The monocyte phenotype measured by flow cytometry from PBMCs of patients with different virus infections (acute phase for HTNV infection/n = 20, febrile phase for JEV infection/n = 15, and chronic phase for HBV/n = 18, or HCV infection/n = 18) or healthy individuals (n = 12). HTNV group as control (vs. JEV, HBV or HCV), for M1-like monocytes, p = 0.0156/ < 0.0001/ = 0.0006; for M2-like monocytes, p = 0.1917/0.0213/0.001; for classic monocytes, p = 0.7341/0.7878/ 0.2571. Gating strategy is shown in Supplementary Fig. 1a. b Overview of disease stages and severity classification for HFRS. The patient sample number of each disease course with different severity for (c–g) has been listed. c The monocyte (CD11b⁺CD11c⁺) percentage measured by flow cytometry in HFRS patients. Healthy group as control, p < 0.001 (vs. febrile stage)/< 0.001 (vs. hypotensive stage)/ = 0.0002 (vs. oliguric stage). Gating strategy is shown in Supplementary Fig. 1b. The relationship between the proportion of M1-like monocytes (measured by flow cytometry) and HFRS severity (Mild/Moderate vs. Severe/Critical) is analyzed either across the whole disease stage (d, p = 0.0787) or at distinct disease phases (e, p = 0.0237, at febrile stage/0.0218, at hypotensive stage/0.1251 at oliguric stage/0.8627 at diuretic stage). Gating strategy is shown in Supplementary Fig. 1a. f Heatmap of the 40-multiplex array. Upregulated cytokines are marked red (p < 0.05). The exact p value of each group is shown in the Source Data File. g The secretion of TNFα, IL-10 and IL-8 in monocytes measured by flow cytometry at the acute stage of HFRS. Mild/Moderate vs. Severe/Critical, p < 0.0001 (TNFα⁺ IL-10⁺ IL-8⁺)/<0.0001 (TNFα⁺ IL-10⁺ IL-8^-)/ = 0.0402 (TNFα⁺ IL-10^- IL-8^-)/ = 0.1711 (TNFα^- IL-10⁺ IL-8⁺)/ = 0.8487 (TNFα^- IL-10^- IL-8⁺)/ < 0.0001 (TNFα^- IL-10⁺ IL-8^-)/ = 0.6775 (TNFα⁺ IL-10^- IL-8⁺) of different monocyte phenotypes. Gating strategy is shown in Supplementary Fig. 2b, c. h Dynamic alteration of HFRS monocyte subsets detected by flow cytometry along with disease progression. Gating strategy is shown in Supplementary Fig. 2b, c. Data are shown as the mean ± SD. Analysis is performed using one-way ANOVA (a, c, Dunnett’s multiple comparisons test), or two-sided unpaired Student’s t test (d–g). *p < 0.05, **p < 0.01, ***p < 0.001; NS no significance. Source data are provided as a Source Data file.