Journal: Immunity

Article Title: Deep spatial profiling of human COVID-19 brains reveals neuroinflammation with distinct microanatomical microglia-T-cell interactions

doi: 10.1016/j.immuni.2021.06.002

Figure Lengend Snippet: Highly multiplexed imaging mass cytometry analysis of COVID-19 brains reveals neuroinflammation (A) Experimental workflow. Medulla oblongata tissue slices from patient autopsies with COVID-19 (n = 25), history of ECMO therapy (n = 5), or multiple sclerosis (n = 6); control patients (n = 5); and COVID-19 olfactory bulb tissue slices (n = 11) were analyzed by IHC and IMC. (B) Exemplary visualization of corresponding COVID-19 medulla tissue by IHC (left) and IMC (right). The area of interest is magnified in the insert. Scale bars: 100 μm and 50 μm. Left: IHC for Iba1 (brown) and CD8 (pink), counterstained with hematoxylin (blue). Arrows indicate CD8 + T cells. Right: Iba1 (red), CD8 (green), collagen (light blue), CD163 (yellow), and histone H3 (blue) IMC data channels are visualized. (C) Exemplary visualization of indicated marker expression IMC data from channels in the same area as (B). Scale bar: 50 μm. (D) Manual cell counting of defined immune populations was performed on the IMC dataset and compared among control (black), ECMO (gray), COVID-19 (blue), and multiple sclerosis patients (purple). Bar graphs indicate means ± SEM. (E) Immunohistochemical reaction for APP (brown), indicating axonal damage in control and COVID-19 medullae. Counterstaining with hematoxylin (blue). Scale bars: 100 μm; 10 μm in the inserts. Right: quantification of APP deposits is shown; bar graph indicates means ± SEM. See also Figure S1 .

Article Snippet: Cytometry analysis platform OMIQ , OMIQ, Inc. , https://www.omiq.ai/.

Techniques: Imaging, Mass Cytometry, Control, Marker, Expressing, Cell Counting, Immunohistochemical staining

Journal: Immunity

Article Title: Deep spatial profiling of human COVID-19 brains reveals neuroinflammation with distinct microanatomical microglia-T-cell interactions

doi: 10.1016/j.immuni.2021.06.002

Figure Lengend Snippet: Spatial profiling of the brain immune response in COVID-19 indicates localized and orchestrated adaptive immune infiltration (A) High-dimensional annotated cell clusters were compared across patients and controls. Immune cell clusters with significantly different abundances in COVID-19 and control patients are shown by scattered dot plots with bar graphs indicating means ± SEM; each dot represents one patient. (B) Spatial interactions between each pair of cell types in patients with COVID-19 were analyzed by permutation-based neighborhood analysis. The percentages of images with significant neighborhood interactions are displayed as a hierarchically clustered heatmap, ranging from −0.4 (avoidance) to +1 (interaction). Rows represent the neighborhood of a cell phenotype of interest. Columns indicate the enrichment or depletion of a cell in other neighborhoods. (C) Cluster c19 spatial neighborhood interactions were determined in COVID-19 and control patients. Columns indicate significant enrichment or depletion of c19 cells in the vicinity of cells from clusters c1–c34. (D) Distance of cluster c19 cells (blue dots) to the nearest collagen + or CD34 + vessel was determined in COVID-19 brain sections and compared with a random distribution. The 25th, 50th, and 75th percentiles are depicted. (E) CD8 T cell activation in the brains of patients with COVID-19. Cluster c19 cells were analyzed for markers of T cell activation, differentiation, exhaustion, and function. Absolute cell counts were compared among patient groups and visualized by boxplots; dots represent samples. (F) CD8 T cells isolated from medulla, olfactory bulb, cortex, and regional lymph node of a deceased COVID-19 patient were analyzed by suspension-mode mass cytometry. CD8 T cell heterogeneity is shown on a t-SNE map; expression of indicated exhaustion markers is indicated by heatmap coloring. Frequencies are illustrated by bar graphs. See also Figure S4 .

Article Snippet: Cytometry analysis platform OMIQ , OMIQ, Inc. , https://www.omiq.ai/.

Techniques: Control, Activation Assay, Isolation, Suspension, Mass Cytometry, Expressing

Journal: Immunity

Article Title: Deep spatial profiling of human COVID-19 brains reveals neuroinflammation with distinct microanatomical microglia-T-cell interactions

doi: 10.1016/j.immuni.2021.06.002

Figure Lengend Snippet:

Article Snippet: Cytometry analysis platform OMIQ , OMIQ, Inc. , https://www.omiq.ai/.

Techniques: Recombinant, Purification, Functional Assay, Control, Blocking Assay, Modification, Microscopy, Staining, Antibody Labeling, Mass Cytometry, Software, Cytometry, Plasmid Preparation