Glycan recognition by collectin-11 drives SARS-CoV-2 infectivity and membrane injury of respiratory epithelial cells
SARS-CoV-2 respiratory-tract infection affects both vaccinated and unvaccinated persons suggesting factors besides adaptive immunity are operative. We investigated the role of collectin-11 (CL-11), an epithelial-secreted carbohydrate-binding lectin that drives innate immunity and eliminates pathogens by complement activation. SARS-CoV-2, despite binding CL-11 to activate complement, was resistant to lysis. Remarkably, opsonization by CL-11 enhanced virus production by infected respiratory epithelial cells independently of complement. Furthermore, infected cells expressing SARS-CoV-2 spike protein displayed enhanced vulnerability to CL-11 binding and membrane attack by complement. The mechanism of enhanced infectivity was ablated in the presence of L-fucose, which occupied the extended carbohydrate-binding cleft of CL-11 in a crystallographic analysis of complexes between L-fucose and CL-11. Our study suggests pathogenicity of SARS-CoV-2 is related to complement-resistance together with enhanced infectivity and injury of respiratory epithelial cells mediated by locally released CL-11.
Authors
- Rocío T. Martínez-Núñez (ORCID: https://orcid.org/0000-0003-2507-4738)
- Hataf Khan (ORCID: https://orcid.org/0000-0003-1128-0266)
- Linda S. Klavinskis (ORCID: https://orcid.org/0000-0001-5828-6978)
- Anastasia Polycarpou (ORCID: https://orcid.org/0000-0002-1797-3787)
- Katie J. Doores (ORCID: https://orcid.org/0000-0002-5507-1725)
- Mona Bafadhel (ORCID: https://orcid.org/0000-0002-9993-2478)
- Jonathan Baker (ORCID: https://orcid.org/0000-0002-9694-8001)
- Tara Wagner-Gamble (ORCID: https://orcid.org/0000-0003-3608-2880)
- Conrad A. Farrar (ORCID: https://orcid.org/0000-0001-9627-9293)
- Marco Romano (ORCID: https://orcid.org/0000-0001-6089-5828)
- Yusun Jeon (ORCID: https://orcid.org/0000-0001-5031-8656)
- Lauren O’Neill
- Roseanna Greenlaw
- Steven H. Sacks (ORCID: https://orcid.org/0000-0001-6361-9095)
- Russell Wallis (ORCID: https://orcid.org/0000-0002-8705-5295)
- Michael H. Malim (ORCID: https://orcid.org/0000-0002-7699-2064)
- Alanoud Alrehaili
- Dorota Smolarek (ORCID: https://orcid.org/0000-0002-3259-1939)
- Varsha Kanabar
Institutions
- University of Leicester (GB)
- King's College - North Carolina (US)
- King's College London (GB)
- King's College School (GB)
- St Peter's Hospital (US)
Publication Details
- Journal
- Proceedings of the National Academy of Sciences
- Published
- 2025-10-24
- DOI
- https://doi.org/10.1073/pnas.2521209122
- Primary Topic
- Complement system in diseases
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Cooley's Anemia Foundation
- Wellcome Trust
- National Institute for Health and Care Research
- British Society for Antimicrobial Chemotherapy
- University of Leicester
- Imperial College London
- King's College London
- University of Oxford
- Public Health England
- Menzies Centre for Australian Studies, King's College London, University of London