Thorax · 2026
Single-cell mapping reveals CXCL11 as a driver of mucus production and inflammation in influenza A virus exacerbation in COPD.
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Melo-Narvaez Maria Camila, Eger Christian, Bertrams Wilhelm, Benedikter Birke J, Ling Feng, Jones Matthew R, Jung Anna Lena, Pauck Kim, Weckler Barbara Christine, Pott Hendrik, Procida-Kowalski Tara, Wilhelm Jochen, Vollmeister Evelyn, Garn Holger, Kirschbaum Andreas, Rohde Gernot, Wygrecka Malgorzata, Nawroth Janna, Talavera-López Carlos, Schmeck Bernd, Lehmann Mareike
Аннотация
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.