Glycan recognition by collectin-11 drives SARS-CoV-2 infectivity and membrane injury of respiratory epithelial cells
Abstract
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.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (19)
Anastasia Polycarpou
Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College
Tara Wagner-Gamble
Department of Infectious Diseases, School of Immunology and Microbial Sciences, King’s College London
Roseanna Greenlaw
Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College
Lauren O’Neill
Department of Infectious Diseases, School of Immunology and Microbial Sciences, King’s College London
Varsha Kanabar
Department of Infectious Diseases, School of Immunology and Microbial Sciences, King’s College London
Alanoud Alrehaili
Department of Respiratory Sciences, University of Leicester
Yusun Jeon
Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College
Jonathan Baker
King’s Centre for Lung Health, School of Immunology and Microbial Sciences, King’s College London
Mona Bafadhel
King’s Centre for Lung Health, School of Immunology and Microbial Sciences, King’s College London
Hataf Khan
Department of Infectious Diseases, School of Immunology and Microbial Sciences, King’s College London
Michael H. Malim
Department of Infectious Diseases, School of Immunology and Microbial Sciences, King’s College London
Marco Romano
Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College
Conrad A. Farrar
Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College
Dorota Smolarek
Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College
Rocio Martinez-Nunez
Department of Infectious Diseases, School of Immunology and Microbial Sciences, King’s College London
Katie J. Doores
Department of Infectious Diseases, School of Immunology and Microbial Sciences, King’s College London
Russell Wallis
Department of Respiratory Sciences, University of Leicester
Linda S. Klavinskis
Department of Infectious Diseases, School of Immunology and Microbial Sciences, King’s College London
Steven H. Sacks
Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College