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

## TL;DR

Sputum from people with primary ciliary dyskinesia causes macrophages to adopt a pro-resolution, phagocytic M2-like state, which may influence lung disease progression.

## Contribution

This study reveals that PCD sputum drives M2-like macrophage polarization, offering new insights into the immune response in PCD-related bronchiectasis.

## Key findings

- PCD sputum increased macrophage phagocytosis and M2 surface markers like CD163 and CD206.
- PCD sputum reduced secretion of proinflammatory cytokines IL-6 and IL-1β.
- M1 markers CD40 and CD80 were downregulated in macrophages exposed to PCD sputum.

## Abstract

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.

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.

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.

PCD sputum induced a phagocytosis prone, M2-like phenotype in healthy macrophages.

The online version contains supplementary material available at 10.1007/s00408-025-00868-6.