Dysregulated antiviral immune response in NK cells, CD8⁺ T cells, and neutrophils in participants with the LGR6 variant. (A-B) Whole blood from participants with the rs74355478 variant in LGR6 (variant group) and controls (control group) was incubated with antibodies against lineage markers to identify NKs (A; CD3^–CD56⁺) and CD8⁺ T cells (C; CD3⁺CD8⁺), and the LGR6 expression was determined using flow cytometry and fluorescently conjugated antibody against this receptor; histogram of the expression of LGR6 (left); whisker plots representing the number of cells expressing LGR6 (right). NK (C), CD8⁺ T cells (D), and neutrophils (E) from participants from the variant and control groups were isolated from whole blood and incubated with various TLR agonists to elicit an antiviral response. Cytokine expression was assessed using flow cytometry with fluorescently conjugated antibodies targeting these proteins. Cells were incubated with class-A CpG (top; TLR9 ligand), Poly (I:C) (middle; TLR3 ligand), R848 (bottom; TLR7/8 ligand) or nonstimulus (NS; vehicle). The colored heat map presents changes in cytokine expression, expressed as the percentage of change of the log of the MFI, between stimulated and NS cells within the same group (left); significant differences from NS controls are denoted in the heat maps; whisker plots depict statistically significant differences in cytokine expression (percentage of change of log MFI against the NS) between the variant and control groups (right). Statistical differences were determined using the Mann-Whitney test (Student t test for log normalized MFI, after normality check using Shapiro test), and P values are displayed. Results are representative of 4 for variants and 5 for controls.