Cystic fibrosis as a modulable model for host – microorganism interactions in airway disease.

01 January 2023 → 31 December 2026
Research Foundation - Flanders (FWO)
Research disciplines
  • Medical and health sciences
    • Respiratory medicine
    • Inflammation
    • Immunology not elsewhere classified
    • Microbiology not elsewhere classified
    • Respiratory medicine
Host - microorganism interactions Airway inflammation Cystic fibrosis
Project description

The pathophysiology of inflammatory airway diseases and their exacerbations is determined by a continuous interplay of (1) airway microenvironment, (2) its microbial co-inhabitants, and (3) host immune response. The cystic fibrosis transmembrane conductance regulator (CFTR) gene encodes for an ion channel involved in the pathogenesis of many chronic airway diseases. In cystic fibrosis (CF), an autosomal recessive trait in CFTR leads to thick and sticky mucus, a defect that can now be (partially) restored at protein level by CFTR modulators in CF patients. We hypothesize that CFTR modulation substantially changes host – microorganism interactions, leading to (1) improved mucociliary clearance and attenuated airway inflammation, (2) decreased virulence of airway microorganisms, and (3) more balanced systemic immune responses. Blood and sputum samples from CF patients are collected before and after introduction of (different levels of) CFTR modulation into our existing prospective biobank. We will assess the role of CFTR on (1) airway microenvironment, (2) microbial behaviour, and (3) host immune response. Through this integrated approach, CF patients in whom CFTR modulator therapy is being stepwise introduced, will serve as the basis to study mechanisms of airway inflammation and host – microorganism interactions in the context of chronic microbial exposure, relevant to other airway diseases such as asthma, chronic obstructive pulmonary disease, and bronchiectasis.