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, Cristiana; Bromuro, Carla; Vendetti, Silvia; Torosantucci, Antonella; Cauda, Roberto; Cassone, Antonio; Palma, Carla

doi:10.3390/v16040497

Open AccessArticle

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

by

Cristiana Barbati

^1,†,

Carla Bromuro

^1,†,

Silvia Vendetti

¹,

Antonella Torosantucci

^1,‡,

Roberto Cauda

²

,

Antonio Cassone

^3,*,§ and

Carla Palma

^1,*,§

¹

Department of Infectious Diseases, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy

²

Dipartimento Salute e Bioetica, Sezione Malattie Infettive, Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli, 8, 00136 Rome, Italy

³

Polo d’Innovazione della Genomica, Genetica e Biologia, Strada del Petriccio e Belriguardo 35, 53100 Siena, Italy

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work and share first authorship.

^‡

Now retired.

^§

These authors contributed equally to this work and share last authorship.

Viruses 2024, 16(4), 497; https://doi.org/10.3390/v16040497

Submission received: 14 January 2024 / Revised: 12 March 2024 / Accepted: 22 March 2024 / Published: 24 March 2024

(This article belongs to the Section Coronaviruses)

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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 the 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.

Keywords: SARS-CoV-2 spike proteins; PBMC; immunomodulation; IL-6; IFN-γ; T cell mitogen; mannose receptor (CD206)

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MDPI and ACS Style

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. https://doi.org/10.3390/v16040497

AMA Style

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(4):497. https://doi.org/10.3390/v16040497

Chicago/Turabian Style

Barbati, Cristiana, Carla Bromuro, Silvia Vendetti, Antonella Torosantucci, Roberto Cauda, Antonio Cassone, and Carla Palma. 2024. "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 16, no. 4: 497. https://doi.org/10.3390/v16040497

APA Style

Barbati, C., Bromuro, C., Vendetti, S., Torosantucci, A., Cauda, R., Cassone, A., & Palma, C. (2024). 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, 16(4), 497. https://doi.org/10.3390/v16040497

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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

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