Establishment of a 3D-Printed Tissue-on-a-Chip Model for Live Imaging of Bacterial Infections.

Despite advances in healthcare, bacterial pathogens remain a severe global health threat, exacerbated by rising antibiotic resistance. Lower respiratory tract infections, with their high death toll, are of particular concern. Accurately replicating host-pathogen interactions in laboratory models is crucial for understanding these diseases and evaluating new therapies.

Metabolic specialization drives reduced pathogenicity in Pseudomonas aeruginosa isolates from cystic fibrosis patients.

Metabolism provides the foundation for all cellular functions. During persistent infections, in adapted pathogenic bacteria metabolism functions radically differently compared with more naïve strains. Whether this is simply a necessary accommodation to the persistence phenotype or if metabolism plays a direct role in achieving persistence in the host is still unclear.

Cross-talk of inflammatory mediators and airway epithelium reveals the cystic fibrosis transmembrane conductance regulator as a major target.

Airway inflammation, mucus hyperproduction and epithelial remodelling are hallmarks of many chronic airway diseases, including asthma, COPD and cystic fibrosis. While several cytokines are dysregulated in these diseases, most studies focus on the response of airways to interleukin (IL)-4 and IL-13, which have been shown to induce mucus hyperproduction and shift the airway epithelium towards a hypersecretory phenotype. We hypothesised that other cytokines might induce the expression of chloride (Cl) channels/transporters, and regulate epithelial differentiation and mucus production.

Impact of KLF4 on Cell Proliferation and Epithelial Differentiation in the Context of Cystic Fibrosis.

Cystic fibrosis (CF) cells display a more cancer-like phenotype vs. non-CF cells. KLF4 overexpression has been described in CF and this transcriptional factor acts as a negative regulator of wt-CFTR.

TMEM16A chloride channel does not drive mucus production.

Airway mucus obstruction is the main cause of morbidity in cystic fibrosis, a disease caused by mutations in the CFTR Cl channel. Activation of non-CFTR Cl channels such as TMEM16A can likely compensate for defective CFTR. However, TMEM16A was recently described as a key driver in mucus production/secretion.