Fig. 10

The proposed mechanism of sustained inflammation in PCD. 1 Due to ciliary immotility in PCD, the mucus is not cleared efficiently, leading to increased numbers of pathogens remaining in the airway and establishing an infection. 2 The trapped airway pathogens trigger an acute inflammatory reaction, attracting neutrophils to the airways. Upon transmigration from the blood, the neutrophils become activated, a process accompanied by a change in surface marker expression, including loss of CD62L and CD16, and an increase in CD11b and CD66b. 3 Once in the airways, neutrophils employ different strategies to combat the pathogens, including the release of enzymes (e.g. myeloperoxidase and neutrophil elastase) and neutrophil extracellular traps (NETs). Part of the neutrophils will die through NETosis, whereas the rest of the neutrophils will go in apoptosis. 4 Due to defective mucociliary clearance, excessive numbers of apoptotic cells, as well as DNA and neutrophil-derived enzymes, remain in the airways. The apoptotic neutrophils attract pro-resolving macrophages to clear the dead cells and initiate the resolution of inflammation. 5 Proteases remaining in the airways inhibit the clearance of apoptotic cells by macrophages through receptor cleavage. 6 Neutrophil-derived molecules damage airway cells, aggravating the inflammation and facilitating secondary infection. Created with www.BioRender.com