ArticleeLife2021
SARS-CoV-2 spike protein induces inflammation via TLR2-dependent activation of the NF-κB pathway.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 279 papers, 5 of them syntheses that pooled it.
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Who cites it
279 citing papers in PubMed, 5 syntheses or guidelines pooled it, 380 citations in OpenAlex.
- Toll-like receptors polymorphisms and COVID-19: a systematic review.Molecular and cellular biochemistry · 2025Pooled it
- Mucosal immune response in biology, disease prevention and treatment.Signal transduction and targeted therapy · 2025Pooled it
- Rare COVID-19 vaccine side effects got lost in the shuffle. Primary cutaneous lymphomas following COVID-19 vaccination: a systematic review.Frontiers in medicine · 2024Pooled it
- The Vitamin D Serum Levels in Pregnant Women Affected by COVID-19: A Systematic Review and Meta-Analysis.Nutrients · 2023Pooled it
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- Glycosylation modulation as a therapeutic strategy for neuroinflammatory disorders: The potential of Tanshinone IIA.iScience · 2026Article
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- Modulation of Host Innate Immune Response by Highly Pathogenic Human Coronaviruses during Viral Infection.Journal of microbiology and biotechnology · 2026Review
- SARS-CoV-2 Nsp1 suppresses the canonical NF-κB pathway by promoting ubiquitin-dependent degradation of TAK1 kinase.PLoS pathogens · 2026Article
- Chemical characterization of Jing Guan Fang and its application in alleviating coronavirus envelope protein-induced proinflammatory responsesJournal of traditional and complementary medicine · 2026Article
- Radiofrequency Fields at 2.45 GHz Reprogram Mitochondria-Lysosome Crosstalk and Modulate the Survival/Death of Macrophages Exposed to LPS and/or the SARS-CoV-2 Spike Protein.International journal of molecular sciences · 2026Article
- COVID-19, the disease that changed the world.Medicine and pharmacy reports · 2026Review
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- Intranasal S-2P and lentinan formulation confers broad protection against SARS-CoV-2 VOCs via IFN-γ-dominant mechanisms.NPJ vaccines · 2026Article
- Mechanistic insights into the impact of prenatal viral infections on maternal and offspring immunity.Npj viruses · 2026Review
- Recombinant SARS-Cov-2 spike protein S1 subunit upregulates P2 × 7-NLRP3 leading to macrophage pyroptosis promoting acute lung injury.Respiratory research · 2026Article
- Spontaneous Remission of Acute Myeloid Leukemia With MutatedCase reports in hematology · 2026Article
- Immunoregulatory effect of metformin in monocytes exposed to SARS-CoV-2 spike protein subunit 1.Immunometabolism (Cobham, Surrey) · 2026Article
219 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.