Alveolar macrophage subtypes express cholesterol and inflammation genes in cystic fibrosis

This study demonstrates up-regulation of alveolar macrophages expressing genes important for inflammation and lipid metabolism in people with cystic fibrosis, identifying potential therapeutic targets. Cystic fibrosis (CF) is a genetic disease that causes lung inflammation. Although new treatments have improved the quality of life of people with CF, inflammation remains a problem. Alveolar macrophages have been shown to be important mediators of CF lung inflammation although the interactions between macrophages and other immune cells in CF are poorly understood. To identify and compare the cellular composition between CF and healthy airspace macrophages and monocytes, healthy control and CF subjects underwent bronchoscopy and single-cell RNA sequencing was performed on the BAL fluid. Unbiased clustering identified 12 macrophage subtypes. We found up-regulation of macrophages expressing CDKN1A and LDLR, both of which are known to alter cholesterol metabolism and promote inflammation. Pathway analysis revealed important interactions between macrophages and monocytes in CF that likely contribute to overall inflammation and adaptation of recruited monocytes to the CF lung. Some of the top pathways identified were related to inflammation and lipid metabolism, which may contribute to persistent inflammation in CF. Our results may identify novel potential therapeutic targets to treat CF lung inflammation.