Flagellin shifts 3D bronchospheres towards mucus hyperproduction

Respiratory Research

Yvonne Kohl¹  Christian Herr²  Richard F. Sprott²  Christoph Beisswenger²  Yiwen Yao²  Robert Bals²  Felix Ritzmann²  Frank Langer³  Thomas Tschernig⁴ 

[1] Department Bioprocessing & Bioanalytics, Fraunhofer Institute for Biomedical Engineering;Department of Internal Medicine V – Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University;Department of Thoracic and Cardiovascular Surgery, Saarland University;Institute of Anatomy and Cell Biology, Saarland University;

关键词: Organoids;    Bronchospheres;    Mucus;    PAMPs;    Flagellin;   

DOI  :  10.1186/s12931-020-01486-x

来源: DOAJ

【 摘 要 】

Abstract Cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) are associated with acute and chronic bacterial infections of the lung. Excessive differentiation of basal cells to mucus-producing goblet cells can result in mucus hyperproduction and loss of mucociliary clearance in the airways of CF and COPD patients. Here, we aimed to investigate the effect of pathogen-associated molecular patterns (PAMPs) on the differentiation of human 3D bronchospheres. Primary human bronchial epithelial cells (HBECs) were differentiated to bronchospheres in the presence of bacterial flagellin and LPS and the synthetic Toll-like receptor (TLR) ligands Pam3CSK4 (TLR-2) and polyinosinic:polycytidylic acid (pIC, TLR-3). Electron and fluorescence microscopy showed that the differentiation of bronchospheres associated with the formation of lumina and appearance of cilia within 30 days after seeding. Incubation with flagellin resulted in a decreased formation of lumina and loss of cilia formation. Incubation with Pam3CSK, pIC, and LPS did not significantly affect formation of lumina and ciliation. Mucus production was strongly increased in response to flagellin and, to a lesser degree, in response to Pam3CSK4. Our results indicate that bacterial factors, such as flagellin, drive the differentiation of the respiratory epithelium towards mucus hyperproduction.

【 授权许可】

Unknown