IFN-γ in vivo treatment leads to transcriptional reprogramming of cells and restores functional immunometabolic defects in monocytes from 1 patient with CGD. (A) uniform manifold approximation and projection (UMAP) visualization of 12 136 whole blood cells of 1 patient with CGD before and 4 hours after in vivo Imukine (rIFN-γ) subcutaneous treatment (50 mg/m2 body surface area, with a maximum of 100 mg) profiled with scRNA-seq and colored by cell type. (B) UMAP visualization of cells colored by condition, before (light purple) and 4 hours after (dark purple) in vivo Imukine (rIFN-γ) treatment. (C) Numbers of differentially expressed genes identified as upregulated (red) or downregulated (blue) in neutrophils and CD14+ monocytes. (D) Module score of the HALLMARK gene set “interferon gamma response” in neutrophils and CD14+ monocytes before and after rIFN-γ treatment. (E) Violin plots of selected differentially expressed genes in CD14+ monocytes isolated before and after in vivo rIFN-γ treatment. (F) IL-8 production after 4 hours of stimulation with either medium or PMA (50 ng/mL) in neutrophils from a patient with CGD before and 4 hours after receiving in vivo Imukine (rIFN-γ) subcutaneously. (G) OCR after Mito Stress Test of monocytes isolated from a patient with CGD before and 4 hours after receiving in vivo Imukine (rIFN-γ) subcutaneously. (H) IL-6 production from monocytes after LPS restimulation at day 6 after BCG-training protocol. Monocytes were isolated from 1 patient with CGD before and 4 hours after receiving Imukine (rIFN-γ). Owing to the low number of subjects, statistical analysis could not be performed for this set of experiments. DCs, dendritic cells; DMSO, dimethyl sulfoxide; NK, natural killer; Plt.act., platelet-activated; QC, quality control.