The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3
Abstract
Toll-like receptors (TLRs) are a family of innate immune-recognition receptors that recognize molecular patterns associated with microbial pathogens, and induce antimicrobial immune responses. Double-stranded RNA (dsRNA) is a molecular pattern associated with viral infection, because it is produced by most viruses at some point during their replication. Here we show that mammalian TLR3 recognizes dsRNA, and that activation of the receptor induces the activation of NF-kappaB and the production of type I interferons (IFNs). TLR3-deficient (TLR3-/-) mice showed reduced responses to polyinosine-polycytidylic acid (poly(I:C)), resistance to the lethal effect of poly(I:C) when sensitized with d-galactosamine (d-GalN), and reduced production of inflammatory cytokines. MyD88 is an adaptor protein that is shared by all the known TLRs. When activated by poly(I:C), TLR3 induces cytokine production through a signalling pathway dependent on MyD88. Moreover, poly(I:C) can induce activation of NF-kappaB and mitogen-activated protein (MAP) kinases independently of MyD88, and cause dendritic cells to mature.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“However, several RNA structural features have been described as immunostimulatory due to interactions with various RNA sensors such as Toll-like receptors, RIG-I, and PKR.”
From Sequence-engineered mRNA without chemical nucleoside modifications enables an effective protein therapy in large animals (2015) · cites this paper as [7]
In the citing paper
“Activation of TLR3 signaling by its agonists can induce apoptosis in human cancer cells [29, 33].”
From Ligand dependent restoration of human TLR3 signaling and death in p53 mutant cells (2016) · cites this paper as [33]
In the citing paper
“Through recognition of TLR3 in endosomes or retinoic acid-inducible gene I, melanoma differentiation-associated protein 5, and inflammasomes in the cytoplasm,96, 97, 98, 99 depending on the amount, dsRNAs might overactivate innate immunity and lead to adverse events.”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [96]
In the citing paper
“90.7% efficacy in participants 5 to 11 years of age96”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [96]
Citations
Cites
Defective LPS Signaling in C3H/HeJ and C57BL/10ScCr Mice: Mutations in Tlr4 Gene
Poltorak, A., He, X., Smirnova, I., Liu, M.-Y., Huffel, C. V., Du, X., Birdwell, D., Alejos, E., Silva, M., Galanos, C., et al. (1998) · Science · doi:10.1126/science.282.5396.2085 · Cited by 7,631
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
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
HOW CELLS RESPOND TO INTERFERONS
Stark, G. R., Kerr, I. M., Williams, B. R. G., Silverman, R. H., & Schreiber, R. D. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.227 · Cited by 3,932
Inaba, K., Inaba, M., Romani, N., Aya, H., Deguchi, M., Ikehara, S., Muramatsu, S., & Steinman, R. M. (1992) · The Journal of Experimental Medicine · doi:10.1084/jem.176.6.1693 · Cited by 3,741
Takeuchi, O., Hoshino, K., Kawai, T., Sanjo, H., Takada, H., Ogawa, T., Takeda, K., & Akira, S. (1999) · Immunity · doi:10.1016/s1074-7613(00)80119-3 · Cited by 3,680
The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5
Hayashi, F., Smith, K. D., Ozinsky, A., Hawn, T. R., Yi, E. C., Goodlett, D. R., Eng, J. K., Akira, S., Underhill, D. M., & Aderem, A. A. (2001) · Nature · doi:10.1038/35074106 · Cited by 3,605
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
Unresponsiveness of MyD88-deficient mice to endotoxin.
Kawai, T., Adachi, O., Ogawa, T., Takeda, K., & Akira, S. (1999) · Immunity · doi:10.1016/s1074-7613(00)80086-2 · Cited by 2,367
MyD88 is an adaptor protein in the hToll/IL-1 receptor family signaling pathways.
Medzhitov, R., Preston-Hurlburt, P., Kopp, E., Stadlen, A., Chen, C.-Q., Ghosh, S., & Janeway, C. (1998) · Molecules and Cells · doi:10.1016/s1097-2765(00)80136-7 · Cited by 1,783
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–200 of 1,052
Toll-like receptors stimulate human neutrophil function
Hayashi, F., Means, T. K., & Luster, A. D. (2003) · Blood · doi:10.1182/blood-2003-04-1078 · Cited by 939
Sequence- and target-independent angiogenesis suppression by siRNA via TLR3
Kleinman, M. E., Yamada, K., Takeda, A., Chandrasekaran, V., Nozaki, M., Baffi, J., Albuquerque, R., Yamasaki, S., Itaya, M., Pan, Y., et al. (2008) · Nature · doi:10.1038/nature06765 · Cited by 939
Barrat, F. J., Meeker, T., Gregorio, J. D., Chan, J. H., Uematsu, S., Akira, S., Chang, B., Duramad, O., & Coffman, R. L. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050914 · Cited by 932
Toll-like receptor 3 promotes cross-priming to virus-infected cells
Schulz, O., Diebold, S. S., Chen, M., Näslund, T. I., Nolte, M. A., Alexopoulou, L., Azuma, Y., Flavell, R. A., Liljeström, P., & Sousa, C. R. E. (2005) · Nature · doi:10.1038/nature03326 · Cited by 919
A STING-activating nanovaccine for cancer immunotherapy
Luo, M., Wang, H., Wang, Z., Cai, H., Lu, Z., Li, Y., Du, M., Huang, G., Wang, C., Chen, X., et al. (2017) · Nature Nanotechnology · doi:10.1038/nnano.2017.52 · Cited by 907
RICK/Rip2/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems
Kobayashi, K. S., Inohara, N., Hernandez, L. D., Galán, J. E., Núñez, G., Janeway, C. A., Medzhitov, R. M., & Flavell, R. A. (2002) · Nature · doi:10.1038/416194a · Cited by 888
Type 1 Interferons and the Virus-Host Relationship: A Lesson in Detente
García‐Sastre, A., & Biron, C. A. (2006) · Science · doi:10.1126/science.1125676 · Cited by 880
Critical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral response
Oganesyan, G., Saha, S. K., Guo, B., He, J. Q., Shahangian, A., Zarnegar, B. J., Perry, A. K., & Cheng, G. (2005) · Nature · doi:10.1038/nature04374 · Cited by 881
Therapeutic targeting of innate immunity with Toll-like receptor agonists and antagonists
Kanzler, H., Barrat, F. J., Hessel, E. M., & Coffman, R. L. (2007) · Nature Medicine · doi:10.1038/nm1589 · Cited by 869
Severe impairment of interleukin-1 and Toll-like receptor signalling in mice lacking IRAK-4
Suzuki, N., Suzuki, S., Duncan, G. S., Millar, D. G., Wada, T., Mirtsos, C., Takada, H., Wakeham, A. C., Itié, A., Li, S., et al. (2002) · Nature · doi:10.1038/nature736 · Cited by 861
Kim, C., Ho, D.-H., Suk, J.-E., You, S., Michael, S., Kang, J., Joong Lee, S., Masliah, E., Hwang, D., Lee, H.-J., et al. (2013) · Nature Communications · doi:10.1038/ncomms2534 · Cited by 856
The evolution of seasonal influenza viruses
Petrova, V. N., & Russell, C. A. (2017) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2017.118 · Cited by 889
RIP1 is an essential mediator of Toll-like receptor 3–induced NF-κB activation
Meylan, E., Burns, K., Hofmann, K., Blancheteau, V., Martinon, F., Kelliher, M. A., & Tschopp, J. (2004) · Nature Immunology · doi:10.1038/ni1061 · Cited by 877
IRF3 Mediates a TLR3/TLR4-Specific Antiviral Gene Program
Doyle, S. E., Vaidya, S. A., O’Connell, R. M., Dadgostar, H., Dempsey, P. W., Wu, T., Rao, G., Sun, R., Haberland, M. E., Modlin, R. L., et al. (2002) · Immunity · doi:10.1016/s1074-7613(02)00390-4 · Cited by 847
Impact of Protein Kinase PKR in Cell Biology: from Antiviral to Antiproliferative Action
García, M. A., Gil, J., Ventoso, I., Guerra, S., Domingo, E., Rivas, C., & Esteban, M. (2006) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00027-06 · Cited by 818
The adaptor molecule TIRAP provides signalling specificity for Toll-like receptors
Horng, T., Barton, G. M., Flavell, R. A., & Medzhitov, R. M. (2002) · Nature · doi:10.1038/nature01180 · Cited by 825
AIM2 forms a complex with pyrin and ZBP1 to drive PANoptosis and host defence
Lee, S., Karki, R., Wang, Y., Nguyen, L. N., Kalathur, R., & Kanneganti, T. (2021) · Nature · doi:10.1038/s41586-021-03875-8 · Cited by 807
Biology and pathogenesis of chikungunya virus
Schwartz, O., & Albert, M. L. (2010) · Nature Reviews Microbiology · doi:10.1038/nrmicro2368 · Cited by 815
Commensal bacteria regulate Toll-like receptor 3–dependent inflammation after skin injury
Lai, Y., Di Nardo, A., Nakatsuji, T., Leichtle, A., Yang, Y., Cogen, A. L., Wu, Z.-R., Hooper, L. V., Schmidt, R. R., von Aulock, S., et al. (2009) · Nature Medicine · doi:10.1038/nm.2062 · Cited by 781
Progress in developing cationic vectors for non-viral systemic gene therapy against cancer
Morille, M., Passirani, C., Vonarbourg, A., Clavreul, A., & Benoît, J. (2008) · Biomaterials · doi:10.1016/j.biomaterials.2008.04.036 · Cited by 786
Signaling Pathways Downstream of Pattern-Recognition Receptors and Their Cross Talk
Lee, M. S., & Kim, Y. (2007) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.76.060605.122847 · Cited by 781
Receptors, Mediators, and Mechanisms Involved in Bacterial Sepsis and Septic Shock
van Amersfoort, E. S., van Berkel, T. J. C., & Kuiper, J. (2003) · Clinical Microbiology Reviews · doi:10.1128/cmr.16.3.379-414.2003 · Cited by 755
Viral evasion and subversion of pattern-recognition receptor signalling
Bowie, A., & Unterholzner, L. (2008) · Nature reviews. Immunology · doi:10.1038/nri2436 · Cited by 763
Self-RNA–antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8
Ganguly, D., Chamilos, G., Lande, R., Gregorio, J. D., Meller, S., Facchinetti, V., Homey, B., Barrat, F. J., Żal, T., & Gilliet, M. F. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20090480 · Cited by 777
Tabeta, K., Hoebe, K., Janssen, E. M., Du, X., Georgel, P., Crozat, K., Mudd, S., Mann, N., Sovath, S., Goode, J., et al. (2006) · Nature Immunology · doi:10.1038/ni1297 · Cited by 600
Toll-Like Receptors in Antiviral Innate Immunity
Lester, S. N., & Li, K. (2013) · Journal of Molecular Biology · doi:10.1016/j.jmb.2013.11.024 · Cited by 759
He, S., Liang, Y., Shao, F., & Wang, X. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1116302108 · Cited by 751
Structural Basis of Toll-Like Receptor 3 Signaling with Double-Stranded RNA
Liu, L., Botos, I., Wang, Y., Leonard, J. N., Shiloach, J., Segal, D. M., & Davies, D. R. (2008) · Science · doi:10.1126/science.1155406 · Cited by 733
Cancer vaccines as promising immuno-therapeutics: platforms and current progress
Liu, J., Fu, M., Wang, M., Wan, D., Wei, Y., & Wei, X. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01247-x · Cited by 762
Recognition and Signaling by Toll-Like Receptors
West, A. P., Koblansky, A. A., & Ghosh, S. (2006) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.21.122303.115827 · Cited by 736
Toll‐like receptors and adaptor molecules in liver disease: Update†
Seki, E., & Brenner, D. A. (2008) · Hepatology · doi:10.1002/hep.22306 · Cited by 722
Chieppa, M., Rescigno, M., Huang, A. Y.-C., & Germain, R. N. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20061884 · Cited by 711
Dunne, A., & O'Neill, L. A. J. (2003) · Science Signaling · doi:10.1126/stke.2003.171.re3 · Cited by 761
Sato, S., Sugiyama, M., Yamamoto, M., Watanabe, Y., Kawai, T., Takeda, K., & Akira, S. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.8.4304 · Cited by 730
Kanneganti, T., Body–Malapel, M., Amer, A. O., Park, J., Whitfield, J. R., Franchi, L., Taraporewala, Z. F., Miller, D. J., Patton, J. T., Inohara, N., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m607594200 · Cited by 706
Subcellular Localization of Toll-Like Receptor 3 in Human Dendritic Cells
Matsumoto, M., Funami, K., Tanabe, M., Oshiumi, H., Shingai, M., Seto, Y., Yamamoto, A., & Seya, T. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.6.3154 · Cited by 723
Innate immunity: the missing link in neuroprotection and neurodegeneration?
Nguyen, M. D., Julien, J., & Rivest, S. (2002) · Nature reviews. Neuroscience · doi:10.1038/nrn752 · Cited by 710
Pichlmair, A., & Sousa, C. R. E. (2007) · Immunity · doi:10.1016/j.immuni.2007.08.012 · Cited by 690
Synthetic TLR Agonists Reveal Functional Differences between Human TLR7 and TLR8
Gorden, K. B., Gorski, K. S., Gibson, S. J., Kedl, R. M., Kieper, W. C., Qiu, X., Tomai, M. A., Alkan, Ş. Ş., & Vasilakos, J. P. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.3.1259 · Cited by 690
Guillot, L., Le Goffic, R., Bloch, S., Escriou, N., Akira, S., Chignard, M., & Si-Tahar, M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m410592200 · Cited by 689
TLR3: Interferon induction by double-stranded RNA including poly(I:C)☆
MATSUMOTO, M., & Seya, T. (2008) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2007.11.005 · Cited by 704
Endogenous ligands of Toll-like receptors
Tsan, M., & Gao, B. (2004) · Journal of Leukocyte Biology · doi:10.1189/jlb.0304127 · Cited by 690
Toll-like receptors: key mediators of microbe detection
Underhill, D. M., & Ozinsky, A. (2002) · Current Opinion in Immunology · doi:10.1016/s0952-7915(01)00304-1 · Cited by 685
Maternal gut bacteria promote neurodevelopmental abnormalities in mouse offspring
Kim, S., Kim, H., Yim, Y. S., Ha, S., Atarashi, K., Tan, T. G., Longman, R. S., Honda, K., Littman, D. R., Choi, G. B., et al. (2017) · Nature · doi:10.1038/nature23910 · Cited by 678
Progress towards in Vivo Use of siRNAs
Behlke, M. A. (2006) · Molecular Therapy · doi:10.1016/j.ymthe.2006.01.001 · Cited by 677
Advances in mRNA Vaccines for Infectious Diseases
Zhang, C., Maruggi, G., Shan, H., & Li, J. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00594 · Cited by 696
Bernasconi, N. L., Onai, N., & Lanzavecchia, A. (2003) · Blood · doi:10.1182/blood-2002-11-3569 · Cited by 684
Structure and Function of Toll Receptors and Their Ligands
Gay, N. J., & Gangloff, M. (2007) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.76.060305.151318 · Cited by 690
Longhi, M. P., Trumpfheller, C., Idoyaga, J., Caskey, M. F., de Matos, I. G., Kluger, C., Salazar, A. Μ., Colonna, M., & Steinman, R. M. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20090247 · Cited by 663
Toll-Like Receptors: Linking Innate and Adaptive Immunity
Pasare, C., & Medzhitov, R. M. (2005) · Advances in experimental medicine and biology · doi:10.1007/0-387-24180-9_2 · Cited by 666
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
Rothenfußer, S., Goutagny, N., DiPerna, G., Gong, M., Monks, B. G., Schoenemeyer, A., Yamamoto, M., Akira, S., & Fitzgerald, K. A. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.8.5260 · Cited by 645
Liu, Y., Gu, Y. H., Han, Y., Zhang, Q., Jiang, Z., Zhang, X., Huang, B., Xu, X., Zheng, J., & Cao, X. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.06.021 · Cited by 654
Cutting edge: impaired toll-like receptor expression and function in aging
Renshaw, M., Rockwell, J., Engleman, C., Gewirtz, A., Katz, J., & Sambhara, S. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.9.4697 · Cited by 626
Developing mRNA-vaccine technologies
Schlake, T., Thess, A., Fotin-Mleczek, M., & Kallen, K.-J. (2012) · RNA Biology · doi:10.4161/rna.22269 · Cited by 622
Herpes simplex virus 1 interaction with Toll-like receptor 2 contributes to lethal encephalitis
Kurt‐Jones, E. A., Chan, M., Zhou, S., Wang, J. P., Reed, G. W., Bronson, R. T., Arnold, M. M., Knipe, D. M., & Finberg, R. W. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308057100 · Cited by 622
Radaeva, S., Sun, R., Jaruga, B., Nguyen, V. T., Tian, Z., & Gao, B. (2006) · Gastroenterology · doi:10.1053/j.gastro.2005.10.055 · Cited by 610
Hansdóttir, S., Monick, M. M., Hinde, S. L., Lovan, N., Look, D. C., & Hunninghake, G. W. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.10.7090 · Cited by 612
SIGIRR, a negative regulator of Toll-like receptor–interleukin 1 receptor signaling
Wald, D. N., Qin, J., Zhao, Z., Qian, Y., Naramura, M., Tian, L., Towne, J. E., Sims, J. E., Stark, G. R., & Li, X. (2003) · Nature Immunology · doi:10.1038/ni968 · Cited by 606
Jensen, S., & Thomsen, A. R. (2012) · Journal of Virology · doi:10.1128/jvi.05738-11 · Cited by 604
Crystal Structure of Human Toll-Like Receptor 3 (TLR3) Ectodomain
Choe, J., Kelker, M. S., & Wilson, I. A. (2005) · Science · doi:10.1126/science.1115253 · Cited by 620
Advances in COVID-19 mRNA vaccine development
Fang, E., Liu, X., Li, M., Zhang, Z., Song, L., Zhu, B., Wu, X., Liu, J., Zhao, D., & Li, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00950-y · Cited by 601
Discriminating self from non-self in nucleic acid sensing
Schlee, M., & Hartmann, G. (2016) · Nature reviews. Immunology · doi:10.1038/nri.2016.78 · Cited by 594
Tetherin Inhibits HIV-1 Release by Directly Tethering Virions to Cells
Pérez-Caballero, D., Zang, T. M., Ebrahimi, A., McNatt, M. W., Gregory, D. A., Johnson, M. C., & Bieniasz, P. D. (2009) · Cell · doi:10.1016/j.cell.2009.08.039 · Cited by 590
Vollmer, J., Weeratna, R. D., Payette, P., Jurk, M., Schetter, C., Laucht, M., Wader, T., Tluk, S., Liu, M., Davis, H. L., et al. (2003) · European Journal of Immunology · doi:10.1002/eji.200324032 · Cited by 592
Innate immunity in the lung: how epithelial cells fight against respiratory pathogens
Bals, R., & Hiemstra, P. S. (2004) · European Respiratory Journal · doi:10.1183/09031936.03.00098803 · Cited by 589
Doyle, S., & O'Neill, L. A. J. (2006) · Biochemical Pharmacology · doi:10.1016/j.bcp.2006.07.010 · Cited by 594
Lee, J., Chuang, T., Redecke, V., She, L., Pitha, P. M., Carson, D. A., Raz, E., & Cottam, H. B. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0631696100 · Cited by 594
DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88
Tarallo, V., Hirano, Y., Gelfand, B. D., Dridi, S., Kerur, N., Kim, Y., Cho, W. G., Kaneko, H., Fowler, B. J., Bogdanovich, S., et al. (2012) · Cell · doi:10.1016/j.cell.2012.03.036 · Cited by 592
Toll-like receptors — taking an evolutionary approach
Leulier, F., & Lemaitre, B. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2303 · Cited by 581
How we detect microbes and respond to them: the Toll-like receptors and their transducers
Beutler, B., Hoebe, K. H. N., Du, X., & Ulevitch, R. J. (2003) · Journal of Leukocyte Biology · doi:10.1189/jlb.0203082 · Cited by 592
Pathogen recognition in the innate immune response
Kumar, H., Kawai, T., & Akira, S. (2009) · Biochemical Journal · doi:10.1042/bj20090272 · Cited by 609
Akira, S. (2003) · Current Opinion in Immunology · doi:10.1016/s0952-7915(02)00013-4 · Cited by 602
SARS-CoV-2 Disrupts Splicing, Translation, and Protein Trafficking to Suppress Host Defenses
Banerjee, A. K., Blanco, M. R., Bruce, E. A., Honson, D. D., Chen, L. M., Chow, A., Bhat, P., Ollikainen, N., Quinodoz, S. A., Loney, C., et al. (2020) · Cell · doi:10.1016/j.cell.2020.10.004 · Cited by 583
The immune system and developmental programming of brain and behavior
Bilbo, S. D., & Schwarz, J. M. (2012) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2012.08.006 · Cited by 606
Viral infection switches non-plasmacytoid dendritic cells into high interferon producers
Diebold, S. S., Montoya, M., Unger, H., Alexopoulou, L., Roy, P., Haswell, L. E., Al‐Shamkhani, A., Flavell, R. A., Borrow, P., & Sousa, C. R. E. (2003) · Nature · doi:10.1038/nature01783 · Cited by 582
Links between innate and adaptive immunity via type I interferon
Bon, A. L., & Tough, D. F. (2002) · Current Opinion in Immunology · doi:10.1016/s0952-7915(02)00354-0 · Cited by 582
Nucleic acid recognition by the innate immune system
Barbalat, R., Ewald, S. E., Mouchess, M. L., & Barton, G. M. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-031210-101340 · Cited by 577
Quantitative proteomics reveals subset-specific viral recognition in dendritic cells
Luber, C. A., Cox, J., Lauterbach, H., Fancke, B., Selbach, M., Tschopp, J., Akira, S., Wiegand, M., Hochrein, H., O'Keeffe, M., et al. (2010) · Immunity · doi:10.1016/j.immuni.2010.01.013 · Cited by 576
Pathogen recognition with Toll-like receptors
Kawai, T., & Akira, S. (2005) · Current Opinion in Immunology · doi:10.1016/j.coi.2005.02.007 · Cited by 589
Hemmi, H., Takeuchi, O., Sato, S., Yamamoto, M., Kaisho, T., Sanjo, H., Kawai, T., Hoshino, K., Takeda, K., & Akira, S. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20040520 · Cited by 576
Mibayashi, M., Martínez‐Sobrido, L., Loo, Y., Cardenas, W. B., Gale, M., & García‐Sastre, A. (2006) · Journal of Virology · doi:10.1128/jvi.01265-06 · Cited by 574
Fujihara, M., Muroi, M., Tanamoto, K., Suzuki, T., Azuma, H., & Ikeda, H. (2003) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2003.08.003 · Cited by 580
Role of Toll-Like Receptors in Pathogen Recognition
Janssens, S., & Beyaert, R. (2003) · Clinical Microbiology Reviews · doi:10.1128/cmr.16.4.637-646.2003 · Cited by 575
Design of Noninflammatory Synthetic siRNA Mediating Potent Gene Silencing in Vivo
Judge, A. D., Bola, G., Lee, A. C. H., & MacLachlan, I. (2005) · Molecular Therapy · doi:10.1016/j.ymthe.2005.11.002 · Cited by 571
Virus Inhibition of RIP3-Dependent Necrosis
Upton, J. W., Kaiser, W. J., & Mocarski, E. S. (2010) · Cell Host & Microbe · doi:10.1016/j.chom.2010.03.006 · Cited by 559
Materials engineering for immunomodulation
Hubbell, J. A., Thomas, S. N., & Swartz, M. A. (2009) · Nature · doi:10.1038/nature08604 · Cited by 581
Wong, S. W., Kwon, M.-J., Choi, A. M. K., Kim, H.-P., Nakahira, K., & Hwang, D. H. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.044065 · Cited by 562
The interferon system of teleost fish
Robertsen, B. (2005) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2005.01.010 · Cited by 564
Living in the liver: hepatic infections
Protzer, U., Maini, M. K., & Knolle, P. A. (2012) · Nature reviews. Immunology · doi:10.1038/nri3169 · Cited by 577
Major findings and recent advances in virus–like particle (VLP)-based vaccines
Mohsen, M. O., Zha, L., Cabral‐Miranda, G., & Bachmann, M. F. (2017) · Seminars in Immunology · doi:10.1016/j.smim.2017.08.014 · Cited by 560
Structures of the Toll-like Receptor Family and Its Ligand Complexes
Jin, M. S., & Lee, J. (2008) · Immunity · doi:10.1016/j.immuni.2008.07.007 · Cited by 573
New horizons in adjuvants for vaccine development
Reed, S. G., Tomai, M. A., & Gale, M. (2020) · Current Opinion in Immunology · doi:10.1016/j.coi.2020.08.008 · Cited by 555
Lövgren, T., Eloranta, M., Båve, U., Alm, G. V., & Rönnblom, L. (2004) · Arthritis & Rheumatism · doi:10.1002/art.20254 · Cited by 553
The use of immunostimulants in fish larval aquaculture
Bricknell, I. R., & Dalmo, R. A. (2005) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2005.03.008 · Cited by 550
Querec, T. D., Bennouna, S., Alkan, S., Laouar, Y., Gorden, K. B., Flavell, R. A., Akira, S., Ahmed, R., & Pulendran, B. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20051720 · Cited by 557
Decoding Toll-like receptors: Recent insights and perspectives in innate immunity
Kawai, T., Ikegawa, M., Ori, D., & Akira, S. (2024) · Immunity · doi:10.1016/j.immuni.2024.03.004 · Cited by 593
Recognition of Endogenous Nucleic Acids by the Innate Immune System
Roers, A., Hiller, B., & Hornung, V. (2016) · Immunity · doi:10.1016/j.immuni.2016.04.002 · Cited by 541
McWhirter, S. M., Fitzgerald, K. A., Rosains, J., Rowe, D. C., Golenbock, D. T., & Maniatis, T. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2237236100 · Cited by 542
Extracellular RNA constitutes a natural procoagulant cofactor in blood coagulation
Kannemeier, C., Shibamiya, A., Nakazawa, F., Trusheim, H., Ruppert, C., Markart, P., Song, Y., Tzima, E., Kennerknecht, E., Niepmann, M., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0608647104 · Cited by 535
Metadata
- Authors
- Alexopoulou, L., Holt, A. C., Medzhitov, R., & Flavell, R. A.
- Affiliations
- Yale University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Medzhitov, Ruslan
- Flavell, Richard A.
- Venue
- Nature
- Published
- 2001-10
- Volume
- 413
- Issue
- 6857
- Pages
- 732-738
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2076361525
- Cited by
- 6,129
- References
- 30
- Citations by year
- 2026: 134 · 2025: 156 · 2024: 161 · 2023: 174 · 2022: 203 · 2021: 270 · 2020: 216 · 2019: 203 · 2018: 209 · 2017: 209 · 2016: 219 · 2015: 237 · 2014: 258 · 2013: 279 · 2012: 303
- FWCI
- 66.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- TLR3, double-stranded RNA, NF-κB activation, type I interferon, MyD88, poly(I:C), innate immunity, viral infection, MAPK signaling, dendritic cell maturation, inflammatory cytokines
- MeSH terms
- Amino Acid Sequence, Animals, Antigens, Differentiation, B-Lymphocytes, Cell Line, Cells, Cultured, Galactosamine, Humans, Interferon Type I, Lymphocyte Activation, Macrophages, Membrane Glycoproteins, Molecular Sequence Data, Poly I-C, Receptors, Cell Surface, Receptors, Immunologic, RNA, Double-Stranded, Virus Diseases, Signal Transduction, Cytokines, NF-kappa B, Sequence Homology, Amino Acid, Mitogen-Activated Protein Kinases, Drosophila Proteins, Adaptor Proteins, Signal Transducing, Toll-Like Receptors, Toll-Like Receptor 3, Mice, Myeloid Differentiation Factor 88
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