Fig. 4: Immune response to SARS-CoV-2 infection in the lungs of K18-hACE2 mice.
a,b, Flow cytometric analysis of lung tissues (a) and BAL (b) at 2, 4 and 7 dpi with SARS-CoV-2 (two independent experiments per group; n = 4 for naive mice; n = 7 for 2 dpi; n = 8 for 4 dpi; n = 8 for 7 dpi; one-way ANOVA; P values: *P = 0.0235, **P = 0.02 and ***P = 0.005 (a); *P = 0.0465 and **P = 0.0062 (b)). Bars represent mean values. Asterisks indicate statistical significance as compared with mock infection. DCs, dendritic cells; NK, natural killer. c, Fold change in the gene expression of the indicated cytokines and chemokines, as determined by RT-qPCR, normalized to Gapdh and compared with naive controls in lung homogenates at 2, 4 and 7 dpi (two independent experiments; n = 11 for 2 dpi; n = 15 for 4 dpi; n = 16 for 7 dpi). Dotted horizontal lines indicate the average level of cytokine or chemokine transcript in naive mice. d, Heat maps of cytokine levels, as measured by multiplex platform, in the lung tissues of SARS-CoV-2-infected mice at 2, 4 and 7 dpi. For each cytokine, the fold change was calculated as compared with mock-infected animals and the log2[fold change] was plotted in the corresponding heat map (two independent experiments; n = 9 for naive mice; n = 12 for 2 dpi; n = 13 for 4 dpi; n = 12 for 7 dpi; associated statistics are reported in Extended Data Fig. 5). EPO, erythropoetin; GM-CSF, granulocyte–macrophage colony-stimulating factor; LIF, leukemia inhibitory factor; M-CSF, macrophage colony-stimulating factor; TIMP-1, tissue inhibitor of metalloproteinase 1; VEGF, vascular endothelial growth factor. e,f, Flow cytometric analysis of peripheral blood at 5 dpi in 6-week-old male and female mice following intranasal inoculation with the indicated doses of SARS-CoV-2 or mock infection. e, Cell numbers per ml blood (one independent experiment; n = 3 for naive; n = 3 for 102 p.f.u.; n = 4 for 103 p.f.u.; n = 4 for 104 p.f.u.; n = 4 for 105 p.f.u.; one-way ANOVA; P values: *P = 0.0385, **P = 0.0026 and ***P = 0.0006 (B cells); *P = 0.0259 and **P = 0.002 (CD4+ T cells); *P = 0.0284, **P = 0.0020 and ***P = 0.0002 (CD8+ T cells); *P = 0.0129 and **P = 0.0068 (monocytes)). Bars indicate mean values. f, Frequency of lymphocytes, monocytes and neutrophils (one independent experiment; n = 3 for naive mice; n = 3 for 102 p.f.u.; n = 4 for 103 p.f.u.; n = 4 for 104 p.f.u.; n = 4 for 105 p.f.u.). Bars indicate means ± s.e.m.
