The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
SARS-CoV-2 spike protein induces inflammation via TLR2-dependent activation of the NF-κB pathway
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China
Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., Zhang, L., Fan, G., Xu, J., Gu, X., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30183-5 · Cited by 48,884
A pneumonia outbreak associated with a new coronavirus of probable bat origin
Zhou, P., Yang, X.-L., Wang, X.-G., Hu, B., Zhang, L., Zhang, W., Si, H.-R., Zhu, Y., Li, B., Huang, C.-L., et al. (2020) · Nature · doi:10.1038/s41586-020-2012-7 · Cited by 21,969
Hoffmann, M., Kleine-Weber, H., Schroeder, S., Krüger, N., Herrler, T., Erichsen, S., Schiergens, T. S., Herrler, G., Wu, N.-H., Nitsche, A., et al. (2020) · Cell · doi:10.1016/j.cell.2020.02.052 · Cited by 20,286
Wang, D., Hu, B., Hu, C., Zhu, F., Liu, X., Zhang, J., Wang, B., Xiang, H., Cheng, Z., Xiong, Y., et al. (2020) · JAMA · doi:10.1001/jama.2020.1585 · Cited by 20,148
A new coronavirus associated with human respiratory disease in China
Wu, F., Zhao, S., Yu, B., Chen, Y.-M., Wang, W., Song, Z.-G., Hu, Y., Tao, Z.-W., Tian, J.-H., Pei, Y.-Y., et al. (2020) · Nature · doi:10.1038/s41586-020-2008-3 · Cited by 11,688
COVID-19: consider cytokine storm syndromes and immunosuppression
Mehta, P., McAuley, D. F., Brown, M., Sanchez, E., Tattersall, R. S., & Manson, J. J. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30628-0 · Cited by 9,664
Structure, function and antigenicity of the SARS-CoV-2 spike glycoprotein
Walls, A. C., Park, Y.-J., Tortorici, M. A., Wall, A., McGuire, A. T., & Veesler, D. (2020) · doi:10.1101/2020.02.19.956581 · Cited by 8,586
Pathological findings of COVID-19 associated with acute respiratory distress syndrome
Xu, Z., Shi, L., Wang, Y., Zhang, J., Huang, L., Zhang, C., Liu, S., Zhao, P., Liu, H., Zhu, L., et al. (2020) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(20)30076-x · Cited by 8,545
Endothelial cell infection and endotheliitis in COVID-19
Varga, Z., Flammer, A. J., Steiger, P., Haberecker, M., Andermatt, R., Zinkernagel, A. S., Mehra, M. R., Schuepbach, R. A., Ruschitzka, F., & Moch, H. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30937-5 · Cited by 6,358
Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus
Li, W., Moore, M. J., Vasilieva, N., Sui, J., Wong, S. K., Berne, M. A., Somasundaran, M., Sullivan, J. L., Luzuriaga, K., Greenough, T. C., et al. (2003) · Nature · doi:10.1038/nature02145 · Cited by 5,923
Cited by
Adverse effects of COVID-19 mRNA vaccines: the spike hypothesis
Trougakos, I. P., Terpos, E., Alexopoulos, H., Politou, M., Paraskevis, D., Scorilas, A., Kastritis, E., Andreakos, E., & Dimopoulos, M. A. (2022) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2022.04.007 · Cited by 273
Cell deaths: Involvement in the pathogenesis and intervention therapy of COVID-19
Li, X., Zhang, Z., Wang, Z., Gutiérrez-Castrellón, P., & Shi, H. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01043-6 · Cited by 67
Mangiferin and Taurine Ameliorate MSRV Infection by Suppressing NF-κB Signaling
Dai, C., Yu, L., Wang, Z., Deng, P., Li, L., Gu, Z., He, X., Wang, J., & Yuan, J. (2023) · Microbiology Spectrum · doi:10.1128/spectrum.05146-22 · Cited by 21
Metadata
- Authors
- Khan, S., Shafiei, M. S., Longoria, C., Schoggins, J. W., Savani, R. C., & Zaki, H.
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2021-12-06
- Volume
- 10
- ISSN
- 2050-084X (ISSN-L)
- OpenAlex
- W4225985695
- Cited by
- 398
- References
- 52
- FWCI
- 22.46
- Type
- journal article
- Language
- en
- Open access
- gold
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: SARS-CoV-2 spike protein induces inflammation via TLR2-dependent activation of the NF-κB pathway. https://app.cochat.ai/papers/10.7554/elife.68563
- The paper
- Khan, S., Shafiei, M. S., Longoria, C., Schoggins, J. W., Savani, R. C., & Zaki, H. (2021). SARS-CoV-2 spike protein induces inflammation via TLR2-dependent activation of the NF-κB pathway. eLife. https://doi.org/10.7554/elife.68563
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
