Influenza A virus (IAV)-induced exacerbations are a major contributor to morbidity in chronic obstructive pulmonary disease (COPD), yet the epithelial mechanisms that govern these events remain unknown. We profiled the response to IAV infection of differentiated airway epithelial cells from healthy donors and individuals with COPD at single-cell resolution. The analysis revealed infection-driven shifts across multiple epithelial compartments and distinct alterations in cell-cell communication in COPD, associated with an increased CXCL11 expression. Functional assays demonstrated that CXCL11 augments mucus-associated gene and protein expression, particularly MUC5AC, increases mucus secretion and viscosity and is associated with reduction of virus-related immune pathways. This highlights CXCL11 as a contributor to both mucus hypersecretion and impaired antiviral epithelial responses in COPD exacerbations.
FörderungenDeutsches Zentrum fr Lungenforschung BMBF) Deutsche Forschungsgemeinschaft von Behring Rntgen Foundation HORIZON EUROPE European Research Council Hessisches Ministerium fr Wissenschaft und Kunst National Institute of Health Sciences Bundesministerium fr Bildung und Forschung (Federal Ministry of Education and Research