Defective LPS Signaling in C3H/HeJ and C57BL/10ScCr Mice: Mutations in Tlr4 Gene
Abstract
Mutations of the gene Lps selectively impede lipopolysaccharide (LPS) signal transduction in C3H/HeJ and C57BL/10ScCr mice, rendering them resistant to endotoxin yet highly susceptible to Gram-negative infection. The codominant Lps d allele of C3H/HeJ mice was shown to correspond to a missense mutation in the third exon of the Toll-like receptor-4 gene ( Tlr4 ), predicted to replace proline with histidine at position 712 of the polypeptide chain. C57BL/10ScCr mice are homozygous for a null mutation of Tlr4 . Thus, the mammalian Tlr4 protein has been adapted primarily to subserve the recognition of LPS and presumably transduces the LPS signal across the plasma membrane. Destructive mutations of Tlr4 predispose to the development of Gram-negative sepsis, leaving most aspects of immune function intact.
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LPS is specifically recognized by TLR4.
“It is specifically recognized by TLR4 [6].”
From Prolyl Isomerase Pin1 Protects Mice from Endotoxin Shock (2011) · cites this paper as [6]
LPS signaling is mediated by TLR4, as mutations or deletions of Tlr4 locus completely abolish LPS-mediated signaling.
“LPS signaling is mediated by TLR4 since mutations or deletions of the Tlr4 locus completely abolish LPS-mediated signaling [26], [27].”
From MicroRNA 146a (miR-146a) Is Over-Expressed during Prion Disease and Modulates the Innate Immune Response and the Microglial Activation State (2012) · cites this paper as [26]
TLR4 is important for cytokine release secondary to gram-negative bacterial sepsis.
“For instance, TLR4 is known to be important for cytokine release secondary to gram-negative bacterial sepsis (9).”
From Repeated TLR9 stimulation results in macrophage activation syndrome–like disease in mice (2011) · cites this paper as [9]
Cites
A human homologue of the Drosophila Toll protein signals activation of adaptive immunity
Medzhitov, R., Preston-Hurlburt, P., & Janeway, C. A. J. (1997) · Nature · doi:10.1038/41131 · Cited by 6,137 · see citing works
Lemaître, B., Nicolas, E., Michaut, L., Reichhart, J., & Hoffmann, J. A. (1996) · Cell · doi:10.1016/s0092-8674(00)80172-5 · Cited by 4,027 · see citing works
A MAP Kinase Targeted by Endotoxin and Hyperosmolarity in Mammalian Cells
Han, J., Lee, J. D., Bibbs, L., & Ulevitch, R. J. (1994) · Science · doi:10.1126/science.7914033 · Cited by 2,647 · see citing works
The stress-activated protein kinase subfamily of c-Jun kinases
Kyriakis, J. M., Banerjee, P. T., Nikolakaki, E., Dai, T., Rubie, E. A., Ahmad, M. F., Avruch, J., & Woodgett, J. R. (1994) · Nature · doi:10.1038/369156a0 · Cited by 2,601 · see citing works
Beutler, B., Milsark, I. W., & Cerami, A. (1985) · Science · doi:10.1126/science.3895437 · Cited by 2,369 · see citing works
Self-citationStructure and Function of Lipopolysaccharide Binding Protein
Schumann, R. R., Leong, S. R., Flaggs, G., Gray, P. W., Wright, S. D., Mathison, J. C., Tobias, P. S., & Ulevitch, R. J. (1990) · Science · doi:10.1126/science.2402637 · Cited by 1,672 · see citing works
Toll-like receptor-2 mediates lipopolysaccharide-induced cellular signalling
Yang, R.-B., Mark, M., Gray, A., Huang, A., Xie, M.-H., Zhang, M., Goddard, A., Wood, W., Gurney, A., & Godowski, P. (1998) · Nature · doi:10.1038/26239 · Cited by 1,319 · see citing works
Identity of tumour necrosis factor and the macrophage-secreted factor cachectin
Beutler, B., Greenwald, D., Hulmes, J. D., Chang, M., Pan, Y.-C. E., Mathison, J. C., Ulevitch, R. J., & Cerami, A. (1985) · Nature · doi:10.1038/316552a0 · Cited by 1,132 · see citing works
Self-citationHaziot, A., Ferrero, E., Köntgen, F., Hijiya, N., Yamamoto, S., Silver, J. E., Stewart, C. L., & Goyert, S. M. (1996) · Immunity · doi:10.1016/s1074-7613(00)80254-x · Cited by 732 · see citing works
Trends in Infectious Diseases Mortality in the United States
Pinner, R. W. (1996) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1996.03530270029027 · Cited by 487 · see citing works
Poltorak, A. N., Smirnova, I., He, X., Liu, M.-Y., Huffel, C. V., Birdwell, D., Alejos, E., Silva, M. J., Du, X., Thompson, P., et al. (1998) · Blood Cells Molecules and Diseases · doi:10.1006/bcmd.1998.0201 · Cited by 387 · see citing works
Self-citationGenetic Control of Leucocyte Responses to Endotoxin
Sultzer, B. M. (1968) · Nature · doi:10.1038/2191253a0 · Cited by 376 · see citing works
Tobias, P. S., Soldau, K., & Ulevitch, R. J. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)81700-8 · Cited by 352 · see citing works
Tumor Necrosis Factor: The molecules and Their Emerging Role in Medicine
Beutler, B., Han, J., Kruys, V., & Giroir, B. P. (1992) · Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) · Cited by 326 · see citing works
Self-citationThe 18‐wheeler mutation reveals complex antibacterial gene regulation in Drosophila host defense
Williams, M. J., Rodriguez, A., Kimbrell, D., & Eldon, E. D. (1997) · EMBO Journal · doi:10.1093/emboj/16.20.6120 · Cited by 297 · see citing works
Endotoxin induces rapid protein tyrosine phosphorylation in 70Z/3 cells expressing CD14.
Han, J., Lee, J. D., Tobias, P. S., & Ulevitch, R. J. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)74564-5 · Cited by 292 · see citing works
Geppert, T. D., Whitehurst, C. E., Thompson, P., & Beutler, B. (1994) · Molecular Medicine · doi:10.1007/bf03403535 · Cited by 228 · see citing works
Self-citationThe Primary Role of Lymphoreticnlar Cells in the Mediation of Host Responses to Bacterial Endotoxim
Michalek, S. M., Moore, R. N., McGhee, J. R., Rosenstreich, D. L., & Mergenhagen, S. E. (1980) · The Journal of Infectious Diseases · doi:10.1093/infdis/141.1.55 · Cited by 210 · see citing works
Genetic defect in responsiveness to the B cell mitogen lipopolysaccharide
Coutinho, A., Forni, L., Melchers, F., & Watanabe, T. (1977) · European Journal of Immunology · doi:10.1002/eji.1830070517 · Cited by 171 · see citing works
The Drosophila 18 wheeler is required for morphogenesis and has striking similarities to Toll
Eldon, E. D., Kooyer, S., D'Evelyn, D., Duman‐Scheel, M., Lawinger, P., Botas, J., & Bellen, H. J. (1994) · Development · doi:10.1242/dev.120.4.885 · Cited by 147 · see citing works
Resistance to Salmonellosis in the Chicken Is Linked toNRAMP1and TNCPreprint
Hu, J., Bumstead, N., Barrow, P., Sebastiani, G., Olien, L., Morgan, K. W., & Malo, D. (1997) · Genome Research · doi:10.1101/gr.7.7.693 · Cited by 144 · see citing works
The Response of Recombinant Inbred Strains of Mice to Bacterial Lipopolysaccharides
Watson, J. D., Riblet, R. J., & Taylor, B. A. (1977) · The Journal of Immunology · doi:10.4049/jimmunol.118.6.2088 · Cited by 138 · see citing works
Endotoxin and IL-1 hyporesponsiveness in a patient with recurrent bacterial infections
Kuhns, D. B., Priel, D. A. L., & Gallin, J. I. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.158.8.3959 · Cited by 101 · see citing works
Genetic basis for unresponsiveness to lipopolysaccharide in C57BL/10Cr mice.
Coutinho, A., & Meo, T. (1978) · Immunogenetics · doi:10.1007/bf01843983 · Cited by 101 · see citing works
Characterization of a Congenitally LPS-Resistant, Athymic Mouse Strain
Vogel, S. N., Hansen, C. T., & Rosenstreich, D. L. (1979) · The Journal of Immunology · doi:10.4049/jimmunol.122.2.619 · Cited by 87 · see citing works
Mathison, J. C., Wolfson, E. B., Steinemann, S. K., Tobias, P. S., & Ulevitch, R. J. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116801 · Cited by 79 · see citing works
Chiang, C. C., & Beachy, P. A. (1994) · Mechanisms of Development · doi:10.1016/0925-4773(94)90041-8 · Cited by 39 · see citing works
Genetic Analysis of Generation of Serum Interferon by Bacterial Lipopolysaccharide
Apte, R. N., Ascher, O., & Pluznik, D. H. (1977) · The Journal of Immunology · doi:10.4049/jimmunol.119.6.1898 · Cited by 35 · see citing works
Action of Endotoxin on Lymphoid Cells
Rosenstreich, D. L., Glade, L. M., & Mergenhagen, S. E. (1977) · The Journal of Infectious Diseases · doi:10.1093/infdis/136.supplement.s239 · Cited by 23 · see citing works
(1980) · The Gerontologist · doi:10.1093/geront/20.2.124 · Cited by 1 · see citing works
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Janeway, C. A., & Medzhitov, R. (2002) · Annual Review of Immunology · doi:10.1146/annurev.immunol.20.083001.084359 · Cited by 8,394 · see citing works
Akira, S., & Takeda, K. (2004) · Nature reviews. Immunology · doi:10.1038/nri1391 · Cited by 8,312 · see citing works
A Toll-like receptor recognizes bacterial DNA
Hemmi, H., Takeuchi, O., Kawai, T., Kaisho, T., Sato, S., Sanjo, H., Matsumoto, M., Hoshino, K., Wagner, H., Takeda, K., et al. (2000) · Nature · doi:10.1038/35047123 · Cited by 6,491 · see citing works
Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3
Alexopoulou, L., Holt, A. C., Medzhitov, R., & Flavell, R. A. (2001) · Nature · doi:10.1038/35099560 · Cited by 6,129 · see citing works
Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease
Hugot, J.-P., Chamaillard, M., Zouali, H., Lesage, S., Cézard, J.-P., Belaiche, J., Almer, S., Tysk, C., O'Morain, C. A., Gassull, M., et al. (2001) · Nature · doi:10.1038/35079107 · Cited by 5,591 · see citing works
Raetz, C. R. H., & Whitfield, C. (2002) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.71.110601.135414 · Cited by 4,404 · see citing works
Taganov, K. D., Boldin, M. P., Chang, K.-J., & Baltimore, D. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605298103 · Cited by 4,317 · see citing works
Toll-like receptors and innate immunity
Medzhitov, R. (2001) · Nature Reviews Immunology · doi:10.1038/35100529 · Cited by 4,308 · see citing works
Hoshino, K., Takeuchi, O., Kawai, T., Sanjo, H., Ogawa, T., Takeda, Y., Takeda, K., & Akira, S. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.7.3749 · Cited by 3,374 · see citing works
LPS/TLR4 signal transduction pathway
Lu, Y.-C., Yeh, W.-C., & Ohashi, P. S. (2008) · Cytokine · doi:10.1016/j.cyto.2008.01.006 · Cited by 3,301 · see citing works
Toll-like receptors in innate immunity
Takeda, K. (2004) · International Immunology · doi:10.1093/intimm/dxh186 · Cited by 3,328 · see citing works
Cryopyrin activates the inflammasome in response to toxins and ATP
Mariathasan, S., Weiss, D. S., Newton, K., McBride, J., O'Rourke, K., Roose-Girma, M., Lee, W. P., Weinrauch, Y., Monack, D. M., & Dixit, V. M. (2006) · Nature · doi:10.1038/nature04515 · Cited by 3,080 · see citing works
Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment
Morgan, X. C., Tickle, T. L., Sokol, H., Gevers, D., Devaney, K. L., Ward, D. V., Reyes, J. A., Shah, S. A., LeLeiko, N., Snapper, S. B., et al. (2012) · Genome Biology · doi:10.1186/gb-2012-13-9-r79 · Cited by 2,713 · see citing works
Macrophages, inflammation, and insulin resistance
Olefsky, J. M., & Glass, C. K. (2010) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021909-135846 · Cited by 2,733 · see citing works
The immunopathogenesis of sepsis
Cohen, J. (2002) · Nature · doi:10.1038/nature01326 · Cited by 2,742 · see citing works
Genomic analysis of reactive astrogliosis
Zamanian, J. L., Xu, L., Foo, L. C., Nouri, N., Zhou, L., Giffard, R. G., & Barres, B. A. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.6221-11.2012 · Cited by 2,404 · see citing works
Gut microbiome and health: mechanistic insights
de Vos, W. M., Tilg, H., Van Hul, M., & Cani, P. D. (2022) · Gut · doi:10.1136/gutjnl-2021-326789 · Cited by 2,388 · see citing works
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Fitzgerald, K. A., & Kagan, J. C. (2020) · Cell · doi:10.1016/j.cell.2020.02.041 · Cited by 2,168 · see citing works
TLR4 mutations are associated with endotoxin hyporesponsiveness in humans
Arbour, N. C., Lorenz, E., Schutte, B. C., Zabner, J., Kline, J. N., Jones, M., Frees, K., Watt, J. L., & Schwartz, D. A. (2000) · Nature Genetics · doi:10.1038/76048 · Cited by 2,024 · see citing works
Toll-like Receptor-4 Mediates Lipopolysaccharide-induced Signal Transduction
Chow, J. C., Young, D. W., Golenbock, D. T., Christ, W. J., & Gusovsky, F. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.16.10689 · Cited by 1,924 · see citing works
MicroRNA-155 is induced during the macrophage inflammatory response
O'Connell, R. M., Taganov, K. D., Boldin, M. P., Cheng, G., & Baltimore, D. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610731104 · Cited by 1,866 · see citing works
The history of toll-like receptors - redefining innate immunity
O'Neill, L. A. J., Golenbock, D., & Bowie, A. G. (2013) · Nature reviews. Immunology · doi:10.1038/nri3446 · Cited by 1,765 · see citing works
Peptidoglycan- and Lipoteichoic Acid-induced Cell Activation Is Mediated by Toll-like Receptor 2
Schwandner, R., Dziarski, R., Wesche, H., Rothe, M., & Kirschning, C. J. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.25.17406 · Cited by 1,704 · see citing works
DAMP-sensing receptors in sterile inflammation and inflammatory diseases
Gong, T., Liu, L., Jiang, W., & Zhou, R. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-019-0215-7 · Cited by 1,672 · see citing works
The immune response of Drosophila
Hoffmann, J. A. (2003) · Nature · doi:10.1038/nature02021 · Cited by 1,553 · see citing works
Negative regulation of Toll-like receptor-mediated immune responses
Liew, F. Y., Xu, D., Brint, E. K., & O'Neill, L. A. J. (2005) · Nature Reviews Immunology · doi:10.1038/nri1630 · Cited by 1,509 · see citing works
Disease-Associated Microglia: A Universal Immune Sensor of Neurodegeneration
Deczkowska, A., Keren-Shaul, H., Weiner, A., Colonna, M., Schwartz, M., & Amit, I. (2018) · Cell · doi:10.1016/j.cell.2018.05.003 · Cited by 1,474 · see citing works
Vogl, T., Tenbrock, K., Ludwig, S., Leukert, N., Ehrhardt, C., van Zoelen, M. A. D., Nacken, W., Foell, D., van der Poll, T., Sorg, C., et al. (2007) · Nature Medicine · doi:10.1038/nm1638 · Cited by 1,418 · see citing works
Oligosaccharides of Hyaluronan Activate Dendritic Cells via Toll-like Receptor 4
Termeer, C., Benedix, F., Sleeman, J., Fieber, C., Voith, U., Ahrens, T., Miyake, K., Freudenberg, M., Galanos, C., & Simon, J. C. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20001858 · Cited by 1,378 · see citing works
Self-citationImai, Y., Kuba, K., Neely, G. G., Yaghubian-Malhami, R., Perkmann, T., van Loo, G., Ermolaeva, M., Veldhuizen, R., Leung, Y. H. C., Wang, H., et al. (2008) · Cell · doi:10.1016/j.cell.2008.02.043 · Cited by 1,356 · see citing works
Lee, J. Y., Sohn, K. H., Rhee, S. H., & Hwang, D. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m011695200 · Cited by 1,299 · see citing works
Signal transduction by the lipopolysaccharide receptor, Toll-like receptor-4
Pålsson‐McDermott, E. M., & O'Neill, L. A. J. (2004) · Immunology · doi:10.1111/j.1365-2567.2004.01976.x · Cited by 1,254 · see citing works
The IRF Family Transcription Factors in Immunity and Oncogenesis
Tamura, T., Yanai, H., Savitsky, D., & Taniguchi, T. (2008) · Annual Review of Immunology · doi:10.1146/annurev.immunol.26.021607.090400 · Cited by 1,259 · see citing works
Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs
Olson, J. K., & Miller, S. D. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.6.3916 · Cited by 1,215 · see citing works
Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases
Gilliet, M., Cao, W., & Liu, Y.-J. (2008) · Nature Reviews Immunology · doi:10.1038/nri2358 · Cited by 1,190 · see citing works
Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1β via Ipaf
Miao, E. A., Alpuche-Aranda, C. M., Dors, M., Clark, A. E., Bader, M. W., Miller, S. I., & Aderem, A. (2006) · Nature Immunology · doi:10.1038/ni1344 · Cited by 1,127 · see citing works
Lehnardt, S., Massillon, L., Follett, P., Jensen, F. E., Ratan, R., Rosenberg, P. A., Volpe, J. J., & Vartanian, T. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1432609100 · Cited by 1,052 · see citing works
Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsis
Thimmulappa, R. K. (2006) · Journal of Clinical Investigation · doi:10.1172/jci25790 · Cited by 1,028 · see citing works
Nguyen, M. T. A., Favelyukis, S., Nguyen, A.-K., Reichart, D., Scott, P. A., Jenn, A., Liu-Bryan, R., Glass, C. K., Neels, J. G., & Olefsky, J. M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m706762200 · Cited by 1,035 · see citing works
Michelsen, K. S., Wong, M. H., Shah, P. K., Zhang, W., Yano, J., Doherty, T. M., Akira, S., Rajavashisth, T. B., & Arditi, M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0403249101 · Cited by 1,019 · see citing works
Cross-Presentation, Dendritic Cells, Tolerance and Immunity
Heath, W. R., & Carbone, F. R. (2001) · Annual Review of Immunology · doi:10.1146/annurev.immunol.19.1.47 · Cited by 882 · see citing works
Vaure, C., & Liu, Y. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00316 · Cited by 842 · see citing works
Schaefer, L., Babelova, A., Kiss, E., Hausser, H.-J., Baliova, M., Krzyzankova, M., Marsche, G., Young, M. F., Mihalik, D., Götte, M., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23755 · Cited by 850 · see citing works
Assembly and localization of Toll-like receptor signalling complexes
Gay, N. J., Symmons, M. F., Gangloff, M., & Bryant, C. E. (2014) · Nature Reviews Immunology · doi:10.1038/nri3713 · Cited by 832 · see citing works
Beutler, B. A. (2009) · Blood · doi:10.1182/blood-2008-07-019307 · Cited by 840 · see citing works
Self-citationHuman Toll-Like Receptors Mediate Cellular Activation by <i>Mycobacterium tuberculosis</i>
Means, T. K., Wang, S., Lien, E., Yoshimura, A., Golenbock, D. T., & Fenton, M. J. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.7.3920 · Cited by 804 · see citing works
Vabulas, R. M., Ahmad-Nejad, P., da Costa, C., Miethke, T., Kirschning, C. J., Häcker, H., & Wagner, H. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103217200 · Cited by 805 · see citing works
Why have clinical trials in sepsis failed?
Marshall, J. C. (2014) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2014.01.007 · Cited by 805 · see citing works
HMGB1: Endogenous Danger Signaling
Klune, J. R., Dhupar, R., Cardinal, J., Billiar, T. R., & Tsung, A. (2008) · Molecular Medicine · doi:10.2119/2008-00034.klune · Cited by 762 · see citing works
TREMs in the immune system and beyond
Colonna, M. (2003) · Nature Reviews Immunology · doi:10.1038/nri1106 · Cited by 701 · see citing works
Microglia activation triggers astrocyte-mediated modulation of excitatory neurotransmission
Pascual, O., Ben Achour, S., Rostaing, P., Triller, A., & Bessis, A. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1111098109 · Cited by 693 · see citing works
Sterile inflammation in the liver
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Paik, Y.-H., Schwabe, R. F., Bataller, R., Russo, M. P., Jobin, C., & Brenner, D. A. (2003) · Hepatology · doi:10.1053/jhep.2003.50182 · Cited by 651 · see citing works
Molecular determinants of crosstalk between nuclear receptors and toll-like receptors
Ogawa, S., Lozach, J., Benner, C., Pascual, G., Tangirala, R. K., Westin, S., Hoffmann, A., Subramaniam, S., David, M., Rosenfeld, M. G., et al. (2005) · Cell · doi:10.1016/j.cell.2005.06.029 · Cited by 647 · see citing works
The CNS role of Toll-like receptor 4 in innate neuroimmunity and painful neuropathy
Tanga, F. Y., Nutile-McMenemy, N., & DeLeo, J. A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501634102 · Cited by 634 · see citing works
SOCS1/JAB Is a Negative Regulator of LPS-Induced Macrophage Activation
Kinjyo, I., Hanada, T., Inagaki-Ohara, K., Mori, H., Aki, D., Ohishi, M., Yoshida, H., Kubo, M., & Yoshimura, A. (2002) · Immunity · doi:10.1016/s1074-7613(02)00446-6 · Cited by 630 · see citing works
Paulos, C. M., Wrzesinski, C., Kaiser, Hinrichs, C. S., Chieppa, M., Cassard, L., Palmer, D. C., Boni, A., Muranski, P., Yu, Z., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci32205 · Cited by 586 · see citing works
Toll-like receptors — taking an evolutionary approach
Leulier, F., & Lemaitre, B. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2303 · Cited by 581 · see citing works
Human Toll-like receptor 4 recognizes host-specific LPS modifications
Hajjar, A. M., Ernst, R. K., Tsai, J. H., Wilson, C. B., & Miller, S. I. (2002) · Nature Immunology · doi:10.1038/ni777 · Cited by 579 · see citing works
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Figueiredo, R. T., Fernandez, P. L., Mourao-Sa, D. S., Porto, B. N., Dutra, F. F., Alves, L. S., Oliveira, M. F., Oliveira, P. L., Graça-Souza, A. V., & Bozza, M. T. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m610737200 · Cited by 576 · see citing works
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Gill, R., Tsung, A., & Billiar, T. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.01.006 · Cited by 553 · see citing works
Lee, J. Y., Ye, J., Gao, Z., Youn, H. S., Lee, W. H., Zhao, L., Sizemore, N., & Hwang, D. H. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305213200 · Cited by 524 · see citing works
Ayres, J. S., & Schneider, D. S. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-075030 · Cited by 475 · see citing works
Bile Acids Induce Inflammatory Genes in Hepatocytes
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Moresco, E. M. Y., LaVine, D., & Beutler, B. (2011) · Current Biology · doi:10.1016/j.cub.2011.05.039 · Cited by 500 · see citing works
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Toll–Like Receptor 4 Is Involved in the Mechanism of Early Alcohol–Induced Liver Injury in Mice
Uesugi, T., Froh, M., Arteel, G. E., Bradford, B. U., & Thurman, R. G. (2001) · Hepatology · doi:10.1053/jhep.2001.25350 · Cited by 488 · see citing works
Pattern recognition receptors and central nervous system repair
Kigerl, K. A., de Rivero Vaccari, J. P., Dietrich, W. D., Popovich, P. G., & Keane, R. W. (2014) · Experimental Neurology · doi:10.1016/j.expneurol.2014.01.001 · Cited by 490 · see citing works
Groeger, S., & Meyle, J. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00208 · Cited by 473 · see citing works
TRPA1 channels mediate acute neurogenic inflammation and pain produced by bacterial endotoxins
Meseguer, V., Alpizar, Y. A., Luis, E., Tajada, S., Denlinger, B., Fajardo, O., Manenschijn, J.-A., Fernández-Peña, C., Talavera, A., Kichko, T., et al. (2014) · Nature Communications · doi:10.1038/ncomms4125 · Cited by 479 · see citing works
Toll-like receptor 4 polymorphisms and aspergillosis in stem-cell transplantation
Bochud, P.-Y., Chien, J. W., Marr, K. A., Leisenring, W. M., Upton, A., Janer, M., Rodrigues, S. D., Li, S., Hansen, J. A., Zhao, L. P., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802629 · Cited by 453 · see citing works
Anatomy of a Discovery: M1 and M2 Macrophages
Mills, C. D. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00212 · Cited by 449 · see citing works
Saberi, M., Woods, N.-B., de Luca, C., Schenk, S., Lu, J. C., Bandyopadhyay, G., Verma, I. M., & Olefsky, J. M. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.09.006 · Cited by 456 · see citing works
“Hematopoietic Deletion of Tlr4 Does Affect Peripheral Lineage Distributions To generate mice with a complete knockout of Tlr4 in macrophages and other immune cells, we transplanted irradiated wild-type (WT) C57BL6 mice with bone marrow from Tlr4 (Poltorak et al., 1998) or WT C57BL/10J mice.”
BackgroundMethodZhang, Z., Ohto, U., Shibata, T., Krayukhina, E., Taoka, M., Yamauchi, Y., Tanji, H., Isobe, T., Uchiyama, S., Miyake, K., et al. (2016) · Immunity · doi:10.1016/j.immuni.2016.09.011 · Cited by 461 · see citing works
TLR-Activated B Cells Suppress T Cell-Mediated Autoimmunity
Lampropoulou, V., Hoehlig, K., Roch, T., Neves, P., Gómez, E. C., Sweenie, C. H., Hao, Y., Freitas, A. A., Steinhoff, U., Anderton, S. M., et al. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.7.4763 · Cited by 436 · see citing works
“Mammals possess at least 12 TLR that provide a powerful system to detect a broad range of pathogens including bacteria (2), mycobacteria (3), viruses (4), fungi (5), and helminths (6).”
BackgroundMelmed, G., Thomas, L. S., Lee, N., Tesfay, S. Y., Lukasek, K., Michelsen, K. S., Zhou, Y., Hu, B., Arditi, M., & Abreu, M. T. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.3.1406 · Cited by 431 · see citing works
Chakravarty, S., & Herkenham, M. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.4268-04.2005 · Cited by 396 · see citing works
Toll-like receptor 8 senses degradation products of single-stranded RNA
Tanji, H., Ohto, U., Shibata, T., Taoka, M., Yamauchi, Y., Isobe, T., Miyake, K., & Shimizu, T. (2015) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2943 · Cited by 404 · see citing works
Repeated TLR9 stimulation results in macrophage activation syndrome–like disease in mice
Behrens, E. M., Canna, S. W., Slade, K., Rao, S., Kreiger, P. A., Paessler, M., Kambayashi, T., & Koretzky, G. A. (2011) · Journal of Clinical Investigation · doi:10.1172/jci43157 · Cited by 392 · see citing works
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 · see citing works
Neuroprotective role of the innate immune system by microglia
Glezer, I., Simard, A. R., & Rivest, S. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.02.055 · Cited by 371 · see citing works
Adaptive immune cells temper initial innate responses
Dong Kim, K., Zhao, J., Auh, S., Yang, X., Du, P., Tang, H., & Fu, Y.-X. (2007) · Nature Medicine · doi:10.1038/nm1633 · Cited by 348 · see citing works
Three decades of messenger RNA vaccine development
Verbeke, R., Lentacker, I., De Smedt, S. C., & Dewitte, H. (2019) · Nano Today · doi:10.1016/j.nantod.2019.100766 · Cited by 342 · see citing works
ECSIT is an evolutionarily conserved intermediate in the Toll/IL-1 signal transduction pathway
Kopp, E., Medzhitov, R., Carothers, J., Xiao, C., Douglas, I., Janeway, C. A., & Ghosh, S. (1999) · Genes & Development · doi:10.1101/gad.13.16.2059 · Cited by 334 · see citing works
Bauman, D. R., Bitmansour, A. D., McDonald, J. G., Thompson, B. M., Liang, G., & Russell, D. W. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909142106 · Cited by 329 · see citing works
Sameer, A. S., & Nissar, S. (2021) · BioMed Research International · doi:10.1155/2021/1157023 · Cited by 323 · see citing works
Sex differences in neuroimmunity and pain
Rosen, S., Ham, B., & Mogil, J. S. (2017) · Journal of Neuroscience Research · doi:10.1002/jnr.23831 · Cited by 318 · see citing works
Commensal microbiota is fundamental for the development of inflammatory pain
Amaral, F. A., Sachs, D., Costa, V. V., Fagundes, C. T., Cisalpino, D., Cunha, T. M., Ferreira, S. H., Cunha, F. Q., Silva, T. A., Nicoli, J. R., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711891105 · Cited by 289 · see citing works
Potential Role of Endotoxin as a Proinflammatory Mediator of Atherosclerosis
Stoll, L. L., Denning, G. M., & Weintraub, N. L. (2004) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000147534.69062.dc · Cited by 288 · see citing works
Microbial recognition by Toll-like receptors
Takeda, K., & Akira, S. (2004) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2003.10.002 · Cited by 285 · see citing works
Youn, J. H., Oh, Y. J., Kim, E. S., Choi, J. E., & Shin, J.-S. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.7.5067 · Cited by 281 · see citing works
Sellers, R. S., Clifford, C. B., Treuting, P. M., & Brayton, C. (2012) · Veterinary Pathology · doi:10.1177/0300985811429314 · Cited by 278 · see citing works
Pinhal-Enfield, G., Ramanathan, M., Hasko, G., Vogel, S. N., Salzman, A. L., Boons, G.-J., & Leibovich, S. J. (2003) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63698-x · Cited by 278 · see citing works
Toll-Like Receptor 4 Promotes α-Synuclein Clearance and Survival of Nigral Dopaminergic Neurons
Stefanova, N., Fellner, L., Reindl, M., Masliah, E., Poewe, W., & Wenning, G. K. (2011) · The American Journal of Pathology · doi:10.1016/j.ajpath.2011.04.013 · Cited by 272 · see citing works
Robertson, R. C., Seira Oriach, C., Murphy, K., Moloney, G. M., Cryan, J. F., Dinan, T. G., Paul Ross, R., & Stanton, C. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.07.145 · Cited by 268 · see citing works
Bhattacharyya, S., Brown, D. E., Brewer, J. A., Vogt, S. K., & Muglia, L. J. (2007) · Blood · doi:10.1182/blood-2006-10-048215 · Cited by 249 · see citing works
USP18 lack in microglia causes destructive interferonopathy of the mouse brain
Goldmann, T., Zeller, N., Raasch, J., Kierdorf, K., Frenzel, K., Ketscher, L., Basters, A., Staszewski, O., Brendecke, S. M., Spiess, A., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201490791 · Cited by 223 · see citing works
The essential role of the intestinal microbiota in facilitating acute inflammatory responses
Souza, D. G., Vieira, A. T., Soares, A. C., Pinho, V., Nicoli, J. R., Vieira, L. Q., & Teixeira, M. M. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.6.4137 · Cited by 247 · see citing works
Duffy, D., Rouilly, V., Libri, V., Hasan, M., Beitz, B., David, M., Urrutia, A., Bisiaux, A., LaBrie, S. T., Dubois, A., et al. (2014) · Immunity · doi:10.1016/j.immuni.2014.03.002 · Cited by 242 · see citing works
Pathogen recognition by innate immunity and its signaling
AKIRA, S. (2009) · Proceedings of the Japan Academy, Series B · doi:10.2183/pjab.85.143 · Cited by 240 · see citing works
- Authors
- Poltorak, A., He, X., Smirnova, I., Liu, M.-Y., Huffel, C. V., Du, X., Birdwell, D., Alejos, E., Silva, M., Galanos, C., Freudenberg, M., Ricciardi-Castagnoli, P., Layton, B., & Beutler, B.
- Affiliations
- Howard Hughes Medical Institute (US)
- A. Poltorak, X. He, I. Smirnova, M.-Y. Liu, C. Van Huffel, X. Du, D. Birdwell, E. Alejos, M. Silva, B. Layton, B. Beutler, Howard Hughes Medical Institute and the Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75235–9050 USA. C. Galanos and M. Freudenberg, Max-Planck Institute für Immunobiologie, Freiburg, Germany. P. Ricciardi, CNR–Cellular and Molecular Pharmacology Center, Milan, Italy.
- ORCID
- Venue
- Science
- Published
- 1998-12-11
- Volume
- 282
- Issue
- 5396
- Pages
- 2085-2088
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2129319296
- Cited by
- 7,631
- References
- 30
- Citations by year
- 2026: 110 · 2025: 108 · 2024: 137 · 2023: 158 · 2022: 158 · 2021: 200 · 2020: 194 · 2019: 202 · 2018: 202 · 2017: 225 · 2016: 250 · 2015: 272 · 2014: 320 · 2013: 284 · 2012: 350
- FWCI
- 76.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Keywords
- TLR4, lipopolysaccharide signaling, endotoxin resistance, C3H/HeJ mice, missense mutations, innate immunity
- MeSH terms
- Amino Acid Sequence, Animals, Chromosome Mapping, Cloning, Molecular, Genes, Dominant, Homozygote, Lipopolysaccharides, Macrophages, Membrane Glycoproteins, Mice, Inbred C3H, Mice, Inbred C57BL, Molecular Sequence Data, Receptors, Cell Surface, RNA, Messenger, Signal Transduction, Gram-Negative Bacterial Infections, Point Mutation, Mutation, Missense, Drosophila Proteins, Toll-Like Receptors, Toll-Like Receptor 4, Mice
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