Quorum sensing regulated neutrophil extracellular traps (NETs) dysregulation in chronic obstructive pulmonary disease (COPD): Host-pathogen interplay in Pseudomonas aeruginosa infection.

Chronic Obstructive Pulmonary Disease (COPD) is not a single condition but a spectrum of diseases, which is characterised by airway limitation, mucus hypersecretion, and is further complicated by persistent bacterial infection leading to excessive neutrophil infiltration. Pseudomonas aeruginosa is one of the most commonly isolated pathogens from COPD patients due to its ability to evade host defence by exploiting its quorum sensing (QS) system and virulence factors. Infiltrated neutrophils form Neutrophil Extracellular Traps (NETs), a defence mechanism to trap and kill the microbes in the COPD airway. But when NETs are dysregulated, they can lead to acute lung injury and microbial persistence. In COPD, compromised pathogen clearance and sustained neutrophil activation promote a self-sustaining inflammatory environment that favours chronic airway colonisation and remodelling. Usage of antibiotics and corticosteroids for treating COPD exacerbation is limited due to the emergence of antimicrobial resistance and their inability to modulate host inflammatory responses. Novel approaches targeting QS pathways, as well as host inflammatory components such as Nrf2 and MAPK/NF-κB, show potential in reducing bacterial virulence and lung pathology. This review emphasises therapeutic strategies that move beyond bactericidal approaches, focusing on the modulation of inflammation and virulence in COPD, drawing insights into host immune dysregulation and bacterial adaptation. It further elaborates the mechanistic connection between P. aeruginosa virulence, NET dysregulation, and chronic inflammation in COPD.