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 accessAbstract
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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Cites
Pathogen Recognition and Innate Immunity
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Self-citationDefective LPS Signaling in C3H/HeJ and C57BL/10ScCr Mice: Mutations in Tlr4 Gene
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Self-citationMD-2, a Molecule that Confers Lipopolysaccharide Responsiveness on Toll-like Receptor 4
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Targeted Disruption of the MyD88 Gene Results in Loss of IL-1- and IL-18-Mediated Function
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Endotoxin-tolerant Mice Have Mutations in Toll-like Receptor 4 (Tlr4)
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Cited by
Venkatesh, M., Mukherjee, S., Wang, H., Li, H., Sun, K., Benechet, A. P., Qiu, Z., Maher, L., Redinbo, M. R., Phillips, R. S., et al. (2014) · Immunity · doi:10.1016/j.immuni.2014.06.014 · Cited by 1,066
The molecular basis of the host response to lipopolysaccharide
Bryant, C. E., Spring, D. R., Gangloff, M., & Gay, N. J. (2010) · Nature Reviews Microbiology · doi:10.1038/nrmicro2266 · Cited by 391
Gao, W., Xiong, Y., Li, Q., & Yang, H. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00508 · Cited by 353
Roger, T., Lugrin, J., Le Roy, D., Goy, G., Mombelli, M., Koessler, T., Ding, X. C., Chanson, A.-L., Reymond, M. K., Miconnet, I., et al. (2011) · Blood · doi:10.1182/blood-2010-05-284711 · Cited by 341
Self-citationImmune dysregulation in sepsis: experiences, lessons and perspectives
Cao, M., Wang, G., & Xie, J. (2023) · Cell Death Discovery · doi:10.1038/s41420-023-01766-7 · Cited by 259
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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- 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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