Fig. 3: Fibrin suppresses NK cells and promotes SARS-CoV-2 infection.
From: Fibrin drives thromboinflammation and neuropathology in COVID-19
a, Heat map of selected genes and pathways from bulk RNA-seq analysis of primary mouse NK cells stimulated with fibrin for 4 days in vitro. n = 3 mice. Each lane represents the normalized scaled expression (z score) from each individual mouse (Methods). b, Fibrin-suppressed GO term networks from bulk RNA-seq analysis of primary mouse NK cells. Each circle represents one significantly altered pathway. NES, normalized enrichment score. c, Kinase activities inferred as a z score of phosphorylated substrates from global MS phosphoproteomics analysis of NK cells isolated from PBMCs unstimulated (mock) or treated with fibrin or IL-15 for 1 h. The colours indicate an increase (red) or decrease (blue) in kinase activity. The black bounding boxes indicate a significant shift in kinase-specific substrate regulation. Statistical analysis was performed using a two-tailed z-test (unadjusted P < 0.05) based on the log2-transformed fold changes between n = 8,054 phosphorylation sites derived from 2 (mock), 3 (fibrin) and 2 (IL-15) biologically independent experiments (Methods). d, The NES of selected pathways from GSEA of fibrin-induced genes in NK cells (shown in b) and macrophages (mac.; scRNA-seq data from a previous study21). e, Microscopy analysis of Mac2 and spike in the lungs of Beta-infected WT, Fga–/– and Fggγ390–396A mice given intraperitoneal injection of anti-NK1.1 or IgG2a at a dose of 8 mg per kg body weight. Nuclei were stained with DAPI (blue). Scale bars, 50 μm (Mac2) and 200 μm (spike). Uninfected: n = 4 WT mice; Beta infected: n = 5 mice per group. Statistical analysis was performed using two-way ANOVA with Tukey’s multiple-comparison test. Data are mean ± s.e.m.
