The complement pattern recognition molecule CL-11 promotes invasion and injury of respiratory epithelial cells by SARS-CoV-2.

Polycarpou, A.; Wagner-Gamble, T.; Greenlaw, R.; O'Neill, L. A.; Khan, H.; Malim, M. M.; Romano, M.; Smolarek, D.; Doores, K. J.; Wallis, R.; Klavinskis, L. S.; Sacks, S.

doi:10.1101/2023.12.11.571109

bioRxiv · 10.1101/2023.12.11.571109

The complement pattern recognition molecule CL-11 promotes invasion and injury of respiratory epithelial cells by SARS-CoV-2.

Polycarpou, A.·Wagner-Gamble, T.·Greenlaw, R.·O'Neill, L. A.·Khan, H.·Malim, M. M.·Romano, M.·Smolarek, D.·Doores, K. J.·Wallis, R.·Klavinskis, L. S.·Sacks, S.

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Abstract

Collectin-11 is a soluble C-type lectin produced at epithelial surfaces to initiate pathogen elimination by complement. Given the respiratory epithelium is a source of CL-11 and downstream complement-pathway components, we investigated the potential of CL-11 to impact the pathogenicity of SARS-CoV-2. While the SARS-CoV-2 spike trimer could bind CL-11 and trigger complement activation followed by MAC formation, the virus was resistant to lysis. Surprisingly, virus production by infected respiratory epithelial cells was enhanced by CL-11 opsonisation of virus but this effect was fully inhibited by sugar-blockade of CL-11. Moreover, SARS-CoV-2 spike protein expressed at the bronchial epithelial cell surface was associated with increased CL-11 binding and MAC formation. We propose that SARS-CoV-2 pathogenicity is exacerbated both by resistance to complement and CL-11 driven respiratory cell invasion and injury at the portal of entry. Contrary to expectation, CL-11 blockade could offer a novel approach to limit the pathogenicity of SARS-CoV-2.

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Polycarpou, A., Wagner-Gamble, T., Greenlaw, R., O'Neill, L. A., Khan, H., Malim, M. M., Romano, M., Smolarek, D., Doores, K. J., Wallis, R., Klavinskis, L. S., Sacks, S.. 2023-12-12. The complement pattern recognition molecule CL-11 promotes invasion and injury of respiratory epithelial cells by SARS-CoV-2.. https://doi.org/10.1101/2023.12.11.571109

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