ArticleFrontiers in immunology2024
TLR2/4 are novel activating receptors for SARS-CoV-2 spike protein on NK cells.
Article in Frontiers in immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Hippuric acid contributes to NK-cell activation with dependence on TLR2 in chronic hepatitis B complicated by MASLD.iScience · 2026Article
- Pattern Recognition Receptors (PRRs) Expression and Activation in COVID-19 and Long COVID: From SARS-CoV-2 Escape Mechanisms to Emerging PRR-Targeted Immunotherapies.Microorganisms · 2025Review
- Current Advances and Applications of Animal Models in SARS-CoV-2 Pathogenesis and Vaccine Development.Microorganisms · 2025Review
- The monomeric but not homotrimeric spike protein of SARS-CoV-2 activates TLR4 signaling.Molecular biology reports · 2025Article
- Review
- Soluble SARS-CoV-2 Spike glycoprotein: considering some potential pathogenic effects.Frontiers in immunology · 2025Review
- The innate immune response in SARS-CoV2 infection: focus on toll-like receptor 4 in severe disease outcomes.Frontiers in immunology · 2025Review
- Immunity and Coagulation in COVID-19.International journal of molecular sciences · 2024Review
- The Ambivalence of Post COVID-19 Vaccination Responses in Humans.Biomolecules · 2024Review
- Variants rs3804099 and rs3804100 in theInternational journal of molecular sciences · 2024Article
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: In early infected or severe coronavirus disease 2019 (COVID-19) patients, circulating NK cells are consistently reduced, despite being highly activated or exhausted. The aim of this paper was to establish whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (SP) may directly trigger NK cells and through which receptor(s). Methods: SP-stimulated human NK cells have been evaluated for the expression of activation markers, cytokine release, and cytotoxic activity, as well as for gene expression profiles and NF-kB phosphorylation, and they have been silenced with specific small interfering RNAs. Results: SPs from the Wuhan strain and other variants of concern (VOCs) directly bind and stimulate purified NK cells by increasing activation marker expression, cytokine release, and cytolytic activity, prevalently in the CD56 Conclusions: TLR2 and TLR4 are novel activating receptors for SP in NK cells, suggesting a new role of these cells in orchestrating the pathophysiology of SARS-CoV-2 infection. The pathogenic relevance of this finding is highlighted by the fact that free SP providing NK cell activation is frequently detected in a SARS-CoV-2 inflamed environment and in plasma of infected and long-COVID-19 subjects.
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