Loss of CFTR Function in Macrophages Alters the Cell Transcriptional Program and Delays Lung Resolution of Inflammation

This study performed single-cell RNA sequencing (scRNA-seq) analyses on lung-lavaged cells from macrophage-specific cystic fibrosis (Mac-CF) mice and congenic wild-type (WT) mice that had been challeged with Pseudomonas aeruginsa (PsA) for different time points (1, 3 and 5 days). Differences in global gene transcription were interrogated and compared. Results demonstrate that CFTR loss of function in macrophages altered the cell transcriptional program that mostly affected mitochondrial respiration, immune responses, and cellular antioxidant system. Thus, loss of CFTR function in macrophages influences the cell homeostasis, leading to a dysregulated cellular response to infection that may exacerbate CF lung disease. Overall design: Mac-CF and WT mice were challenged with PsA (2.0x10e7 CFU) for different time points (Days 1, 3 and 5). Then, the assigned animals were sacrificed and their lungs lavaged with PBS (3x 0.8 ml). The lung-lavaged cells were collected and immediately processed for sc-RNA-seq.