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Cited by 269

The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.

Protection from lethal Gram-negative bacterial sepsis by targeting Toll-like receptor 4

Open access
Roger, Thierry, Froidevaux, Céline, Le Roy, Didier, Reymond, Marlies Knaup, Chanson, Anne-Laure, Mauri, Davide, Burns, Kim, Riederer, Beat Michel, Akira, Shizuo, Calandra, Thierry·2009·Proceedings of the National Academy of Sciences

Abstract

Toll-like receptor 4 (TLR4), the signal-transducing molecule of the LPS receptor complex, plays a fundamental role in the sensing of LPS from Gram-negative bacteria. Activation of TLR4 signaling pathways by LPS is a critical upstream event in the pathogenesis of Gram-negative sepsis, making TLR4 an attractive target for novel antisepsis therapy. To validate the concept of TLR4-targeted treatment strategies in Gram-negative sepsis, we first showed that TLR4−/−and myeloid differentiation primary response gene 88 (MyD88)−/−mice were fully resistant to Escherichia coli–induced septic shock, whereas TLR2−/−and wild-type mice rapidly died of fulminant sepsis. Neutralizing anti-TLR4 antibodies were then generated using a soluble chimeric fusion protein composed of the N-terminal domain of mouse TLR4 (amino acids 1–334) and the Fc portion of human IgG1. Anti-TLR4 antibodies inhibited intracellular signaling, markedly reduced cytokine production, and protected mice from lethal endotoxic shock and E. coli sepsis when administered in a prophylactic and therapeutic manner up to 13 h after the onset of bacterial sepsis. These experimental data provide strong support for the concept of TLR4-targeted therapy for Gram-negative sepsis.

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Metadata

Authors
Roger, T., Froidevaux, C., Le Roy, D., Reymond, M. K., Chanson, A.-L., Mauri, D., Burns, K., Riederer, B. M., Akira, S., & Calandra, T.
Venue
Proceedings of the National Academy of Sciences
Published
2009-02-17
Volume
106
Issue
7
Pages
2348-2352
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2007701914
Cited by
269
References
38
FWCI
9.93
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Protection from lethal Gram-negative bacterial sepsis by targeting Toll-like receptor 4. https://app.cochat.ai/papers/10.1073/pnas.0808146106
The paper
Roger, T., Froidevaux, C., Le Roy, D., Reymond, M. K., Chanson, A.-L., Mauri, D., Burns, K., Riederer, B. M., Akira, S., & Calandra, T. (2009). Protection from lethal Gram-negative bacterial sepsis by targeting Toll-like receptor 4. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0808146106

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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.