PT  - JOURNAL ARTICLE
AU  - Kim Chiok
AU  - Kevin Hutchison
AU  - Lindsay Grace Miller
AU  - Santanu Bose
AU  - Tanya A. Miura
TI  - Proinflammatory responses in SARS-CoV-2 infected and soluble spike glycoprotein S1 subunit activated human macrophages
AID  - 10.1101/2021.06.14.448426
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.06.14.448426
4099  - http://biorxiv.org/content/early/2021/06/15/2021.06.14.448426.short
4100  - http://biorxiv.org/content/early/2021/06/15/2021.06.14.448426.full
AB  - Critically ill COVID-19 patients infected with SARS-CoV-2 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 used SARS-CoV-2 infected and glycosylated soluble SARS-CoV-2 Spike S1 subunit (S1) treated THP-1 human-derived macrophage-like cell line 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, virus infection resulted in upregulation of both TNF-α and CXCL10 genes. Our study shows that S1 is a key viral component inducing inflammatory response in macrophages, independently of virus replication. Thus, virus-infected or soluble S1-activated macrophages may become sources of pro-inflammatory mediators contributing to hyperinflammation in COVID-19 patients.Competing Interest StatementThe authors have declared no competing interest.