SARS-CoV-2 immune complex triggers human monocyte necroptosis

Santos, L.; Antunes, K. H.; Cassao, G.; Goncalves, J. I.; Abbadi, B. L.; Bizarro, C. V.; Basso, L. A.; Machado, P.; Souza, A. P. D. d.; Porto, B.

doi:10.1101/2022.10.13.512127

bioRxiv · 10.1101/2022.10.13.512127

SARS-CoV-2 immune complex triggers human monocyte necroptosis

Santos, L.·Antunes, K. H.·Cassao, G.·Goncalves, J. I.·Abbadi, B. L.·Bizarro, C. V.·Basso, L. A.·Machado, P.·Souza, A. P. D. d.·Porto, B.

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Abstract

We analyzed the ability of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) itself and SARS-CoV-2-IgG immune complexes to trigger human monocyte necroptosis. SARS-CoV-2 was able to induce monocyte necroptosis dependently of MLKL activation. Necroptosis-associated proteins (RIPK1, RIPK3 and MLKL) were involved in SARS-CoV-2 N1 gene expression in monocytes. SARS-CoV-2 immune complexes promoted monocyte necroptosis in a RIPK3- and MLKL-dependent manner, and Syk tyrosine kinase was necessary for SARS-CoV-2 immune complex-induced monocyte necroptosis, indicating the involvement of Fc{gamma} receptors on necroptosis. Finally, we provide evidence that elevated LDH levels as a marker of lytic cell death are associated with COVID-19 pathogenesis.

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Santos, L., Antunes, K. H., Cassao, G., Goncalves, J. I., Abbadi, B. L., Bizarro, C. V., Basso, L. A., Machado, P., Souza, A. P. D. d., Porto, B.. 2022-10-14. SARS-CoV-2 immune complex triggers human monocyte necroptosis. https://doi.org/10.1101/2022.10.13.512127

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