Sputum from Individuals with Primary Ciliary Dyskinesia Drives M2-like Macrophage Polarization

INTRODUCTION: Primary ciliary dyskinesia (PCD) is a rare, congenital condition in which impaired ciliary function leads to bronchiectasis and progressive lung function decline. Bronchiectasis development is believed to involve infection and inflammation but is incompletely understood. Macrophages play a central role in cellular immune response, contributing to both pathogen clearance and immunoregulation. Depending on local stimuli, macrophages are polarized towards pro-inflammatory (M1) or pro-resolution/phagocytic (M2) phenotypes. This study aims to investigate the effects of PCD sputum on macrophage polarization. METHODS: Sputum from 27 individuals with PCD and seven healthy controls were used to stimulate healthy monocyte-derived macrophages. Macrophage polarization was determined by surface markers, phagocytic ability and cytokine production using flow cytometry and immunoassays. RESULTS: Macrophages stimulated with PCD sputum exhibited enhanced phagocytosis (MFI 194268 vs. 58235, p = 0.0002), increased expression of M2-associated surface markers CD163, CD206 and CD16, and reduced secretion of proinflammatory cytokines IL-6 (10.38 vs. 113.22 pg/ml, p = 0.0013) and IL-1β (0.75 vs. 3.60 pg/ml, p < 0.0001). Concurrently, expressions of M1-associated surface markers CD40 and CD80 were reduced. CONCLUSION: PCD sputum induced a phagocytosis prone, M2-like phenotype in healthy macrophages.