Proinflammatory Responses in SARS-CoV-2 and Soluble Spike Glycoprotein S1 Subunit Activated Human Macrophages

Chiok, Kim; Hutchison, Kevin; Miller, Lindsay Grace; Bose, Santanu; Miura, Tanya A.

doi:10.3390/v15030754

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Proinflammatory Responses in SARS-CoV-2 and Soluble Spike Glycoprotein S1 Subunit Activated Human Macrophages

by

Kim Chiok

^1,‡

,

Kevin Hutchison

²,

Lindsay Grace Miller

¹,

Santanu Bose

^1,† and

Tanya A. Miura

^2,3,*,†

¹

Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA

²

Department of Biological Sciences, University of Idaho, Moscow, ID 83844, USA

³

Institute for Modeling Collaboration and Innovation, University of Idaho, Moscow, ID 83844, USA

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

^‡

Current affiliation: Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.

Viruses 2023, 15(3), 754; https://doi.org/10.3390/v15030754

Submission received: 18 January 2023 / Revised: 2 March 2023 / Accepted: 10 March 2023 / Published: 15 March 2023

(This article belongs to the Special Issue Cytokines in SARS-CoV-2 Infection)

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Abstract

Critically ill COVID-19 patients display signs of generalized hyperinflammation. Macrophages trigger inflammation to eliminate pathogens and repair tissue, but this process can also lead to hyperinflammation and resulting exaggerated disease. The role of macrophages in dysregulated inflammation during SARS-CoV-2 infection is poorly understood. We inoculated and treated human macrophage cell line THP-1 with SARS-CoV-2 and purified, glycosylated, soluble SARS-CoV-2 spike protein S1 subunit (S1) to clarify the role of macrophages in pro-inflammatory responses. Soluble S1 upregulated TNF-α and CXCL10 mRNAs, and induced secretion of TNF-α from THP-1 macrophages. While THP-1 macrophages did not support productive SARS-CoV-2 replication or viral entry, virus exposure resulted in upregulation of both TNF-α and CXCL10 genes. Our study shows that extracellular soluble S1 protein is a key viral component inducing pro-inflammatory responses in macrophages, independent of virus replication. Thus, virus- or soluble S1-activated macrophages may become sources of pro-inflammatory mediators contributing to hyperinflammation in COVID-19 patients.

Keywords: COVID-19; SARS-CoV-2; hyperinflammation; spike; S1 subunit; macrophages

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MDPI and ACS Style

Chiok, K.; Hutchison, K.; Miller, L.G.; Bose, S.; Miura, T.A. Proinflammatory Responses in SARS-CoV-2 and Soluble Spike Glycoprotein S1 Subunit Activated Human Macrophages. Viruses 2023, 15, 754. https://doi.org/10.3390/v15030754

AMA Style

Chiok K, Hutchison K, Miller LG, Bose S, Miura TA. Proinflammatory Responses in SARS-CoV-2 and Soluble Spike Glycoprotein S1 Subunit Activated Human Macrophages. Viruses. 2023; 15(3):754. https://doi.org/10.3390/v15030754

Chicago/Turabian Style

Chiok, Kim, Kevin Hutchison, Lindsay Grace Miller, Santanu Bose, and Tanya A. Miura. 2023. "Proinflammatory Responses in SARS-CoV-2 and Soluble Spike Glycoprotein S1 Subunit Activated Human Macrophages" Viruses 15, no. 3: 754. https://doi.org/10.3390/v15030754

APA Style

Chiok, K., Hutchison, K., Miller, L. G., Bose, S., & Miura, T. A. (2023). Proinflammatory Responses in SARS-CoV-2 and Soluble Spike Glycoprotein S1 Subunit Activated Human Macrophages. Viruses, 15(3), 754. https://doi.org/10.3390/v15030754

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

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Proinflammatory Responses in SARS-CoV-2 and Soluble Spike Glycoprotein S1 Subunit Activated Human Macrophages

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