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SARS-CoV-2 spike protein induces inflammation via TLR2-dependent activation of the NF-κB pathway
- Source :
- eLife, bioRxiv, article-version (status) pre, article-version (number) 1, eLife, Vol 10 (2021)
- Publication Year :
- 2021
-
Abstract
- The pathogenesis of COVID-19 is associated with a hyperinflammatory response; however, the precise mechanism of SARS-CoV-2-induced inflammation is poorly understood. Here, we investigated direct inflammatory functions of major structural proteins of SARS-CoV-2. We observed that spike (S) protein potently induced inflammatory cytokines and chemokines, including IL-6, IL-1β, TNFα, CXCL1, CXCL2, and CCL2, but not IFNs in human and mouse macrophages. No such inflammatory response was observed in response to membrane (M), envelope (E), and nucleocapsid (N) proteins. When stimulated with extracellular S protein, human and mouse lung epithelial cells also produced inflammatory cytokines and chemokines. Interestingly, epithelial cells expressing S protein intracellularly were non-inflammatory, but elicited an inflammatory response in macrophages when co-cultured. Biochemical studies revealed that S protein triggers inflammation via activation of the NF-κB pathway in a MyD88-dependent manner. Further, such an activation of the NF-κB pathway was abrogated in Tlr2-deficient macrophages. Consistently, administration of S protein-induced IL-6, TNF-α, and IL-1β in wild-type, but not Tlr2-deficient mice. Notably, upon recognition of S protein, TLR2 dimerizes with TLR1 or TLR6 to activate the NF-κB pathway. Taken together, these data reveal a mechanism for the cytokine storm during SARS-CoV-2 infection and suggest that TLR2 could be a potential therapeutic target for COVID-19.
- Subjects :
- Chemokine
QH301-705.5
Science
Inflammation
spike protein
Article
General Biochemistry, Genetics and Molecular Biology
Proinflammatory cytokine
Mice
Immunology and Inflammation
medicine
Animals
Humans
TLR2
Biology (General)
General Immunology and Microbiology
biology
Chemistry
SARS-CoV-2
General Neuroscience
NF-kappa B
COVID-19
General Medicine
medicine.disease
Toll-Like Receptor 2
Cell biology
CXCL1
CXCL2
HEK293 Cells
A549 Cells
inflammation
Spike Glycoprotein, Coronavirus
cytokine storm
Viruses
biology.protein
Medicine
Tumor necrosis factor alpha
medicine.symptom
Cytokine storm
Signal Transduction
Research Article
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- bioRxiv : the preprint server for biology
- Accession number :
- edsair.doi.dedup.....806c2f5c628a8761a76926d15d6f8aac