Single-cell mapping reveals CXCL11 as a driver of mucus production and inflammation in influenza A virus exacerbation in COPD
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.
Authors
- M Lehmann
- M. Camila Melo-Narváez (ORCID: https://orcid.org/0000-0002-6067-3229)
- Barbara Weckler (ORCID: https://orcid.org/0009-0006-7091-1071)
- Malgorzata Wygrecka
- Janna C. Nawroth (ORCID: https://orcid.org/0000-0003-1898-3968)
- Birke J. Benedikter (ORCID: https://orcid.org/0000-0002-1103-2484)
- Andreas Kirschbaum (ORCID: https://orcid.org/0000-0003-4987-8036)
- Evelyn Vollmeister (ORCID: https://orcid.org/0000-0002-0539-7874)
- Kim Pauck (ORCID: https://orcid.org/0009-0002-0756-0142)
- Carlos Talavera‐López (ORCID: https://orcid.org/0000-0001-8590-2393)
- Hendrik Pott (ORCID: https://orcid.org/0000-0002-6842-143X)
- Matthew R. Jones (ORCID: https://orcid.org/0000-0002-2206-7762)
- Anna Lena Jung
- Holger Garn
- Tara Procida-Kowalski
- Feng Ling
- Christian Eger
- Wilhelm Bertrams
- Gernot Rohde
Institutions
- Philipps University of Marburg (DE)
- Justus-Liebig-Universität Gießen (DE)
- University of Würzburg (DE)
- Maastricht University Medical Centre (NL)
- Helmholtz Zentrum München (DE)
- German Center for Lung Research (DE)
- Universities of Giessen and Marburg Lung Center (DE)
- Loewe Center for Synthetic Microbiology (DE)
- Cardio-Pulmonary Institute (DE)
- Technical University of Munich (DE)
Publication Details
- Journal
- Thorax
- Published
- 2026-02-23
- DOI
- https://doi.org/10.1136/thorax-2025-224202
- Primary Topic
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- European Commission
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- Deutsches Zentrum für Lungenforschung
- National Institutes of Health
- HORIZON EUROPE Framework Programme