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The Glycan Ectodomain of SARS-Cov-2 Spike Protein Modulates Cytokine Production and Expression of CD206 Mannose Receptor in PBMC Cultures of Pre-COVID-19 Healthy Subjects
Barbati, C.; Bromuro, C.; Vendetti, S.; Torosantucci, A.; Cauda, R.; Cassone, A.; Palma, C. The Glycan Ectodomain of SARS-CoV-2 Spike Protein Modulates Cytokine Production and Expression of CD206 Mannose Receptor in PBMC Cultures of Pre-COVID-19 Healthy Subjects. Viruses2024, 16, 497.
Barbati, C.; Bromuro, C.; Vendetti, S.; Torosantucci, A.; Cauda, R.; Cassone, A.; Palma, C. The Glycan Ectodomain of SARS-CoV-2 Spike Protein Modulates Cytokine Production and Expression of CD206 Mannose Receptor in PBMC Cultures of Pre-COVID-19 Healthy Subjects. Viruses 2024, 16, 497.
Barbati, C.; Bromuro, C.; Vendetti, S.; Torosantucci, A.; Cauda, R.; Cassone, A.; Palma, C. The Glycan Ectodomain of SARS-CoV-2 Spike Protein Modulates Cytokine Production and Expression of CD206 Mannose Receptor in PBMC Cultures of Pre-COVID-19 Healthy Subjects. Viruses2024, 16, 497.
Barbati, C.; Bromuro, C.; Vendetti, S.; Torosantucci, A.; Cauda, R.; Cassone, A.; Palma, C. The Glycan Ectodomain of SARS-CoV-2 Spike Protein Modulates Cytokine Production and Expression of CD206 Mannose Receptor in PBMC Cultures of Pre-COVID-19 Healthy Subjects. Viruses 2024, 16, 497.
Abstract
The ability of recombinant, SARS-CoV-2 Spike (S) protein to modulate the production of two COVID-19 relevant, pro-inflammatory cytokines (IL-6 and IFN-γ) in PBMC cultures of healthy, pre-Covid-19 subjects was investigated. We observed that cytokine production was largely and diversely modulated by the S protein depending on antigen or mitogen stimulation, as well as on the protein source, insect (S-in) or human (S-hu) cells. While both proteins co-stimulated cytokine production by polyclonally CD3-activated T cells, PBMC activation by the mitogenic lectin Concanavalin A (Con A) was up modulated by S-hu protein and down-modulated by S-in protein. These modulatory effects were likely mediated by the S glycans as demonstrated by direct Con A-S binding experiments and use of yeast mannan as Con A binder. While being ineffective in modulating memory antigenic T cell responses, the S proteins and mannan were able to induce IL-6 production in unstimulated PBMC cultures and upregulate the expression of Mannose Receptor (CD206), a marker of anti-inflammatory M2 macrophage. Our data point to a relevant role of N-glycans, particularly N-mannosidic chains, decorating the S protein in the immunomodulatory effects here reported. These novel biological activities of the S glycan ectodomain may add to the comprehension of Covid-19 pathology and immunity to SARS-CoV-2.
Public Health and Healthcare, Public Health and Health Services
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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