The DOI matches its Crossref record; 131 of the 131 references it cites were found in a registry or an index.
Toll-like receptors — taking an evolutionary approach
Open accessAbstract
The Toll receptor was initially identified in Drosophila melanogaster for its role in embryonic development. Subsequently, D. melanogaster Toll and mammalian Toll-like receptors (TLRs) have been recognized as key regulators of immune responses. After ten years of intense research on TLRs and the recent accumulation of genomic and functional data in diverse organisms, we review the distribution and functions of TLRs in the animal kingdom. We provide an evolutionary perspective on TLRs, which sheds light on their origin at the dawn of animal evolution and suggests that different TLRs might have been co-opted independently during animal evolution to mediate analogous immune functions.
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.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Pleurobrachia also lacks major elements that initiate innate immunity such as pattern recognitionreceptors(Toll-like,Nod-like,RIG-like,Ig-Toll-IL-1Rdomain) andimmunemediators,MyD88andRHDtranscriptionfactors,that are present in bilaterians, cnidarians and, in divergent forms, in sponges 19,20 (Supplementary Table 20).”
From The ctenophore genome and the evolutionary origins of neural systems (2014) · cites this paper as [20]
Experimental — accuracy not yet measured
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
Pathogen Recognition and Innate Immunity
Akira, S., Uematsu, S., & Takeuchi, O. (2006) · Cell · doi:10.1016/j.cell.2006.02.015 · Cited by 12,401
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
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
Lemaître, B., Nicolas, E., Michaut, L., Reichhart, J., & Hoffmann, J. A. (1996) · Cell · doi:10.1016/s0092-8674(00)80172-5 · Cited by 4,224
Toll-like receptor control of the adaptive immune responses
Iwasaki, A., & Medzhitov, R. M. (2004) · Nature Immunology · doi:10.1038/ni1112 · Cited by 4,166
Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8
Heil, F., Hemmi, H., Hochrein, H., Ampenberger, F., Kirschning, C., Akira, S., Lipford, G., Wagner, H., & Bauer, S. (2004) · Science · doi:10.1126/science.1093620 · Cited by 3,947
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
The host defense of Drosophila melanogaster.
Lemaître, B., & Hoffmann, J. (2007) · Annual Review of Immunology · doi:10.1146/annurev.immunol.25.022106.141615 · Cited by 3,404
Research works printed but not linked: 1
- Hultmark, D. Insect lysozymes. EXS 75, 87–102 (1996).
Cited by
Sorted by citations
Items 501–582 of 582
Evolution of the Immune System
Pasquier, L. D. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-95488-4.00037-1 · Cited by 1
Immune cell type divergence in a basal chordatePreprint
Scully, T. D., Pickett, C. J., Gort-Freitas, N. A., Davidson, B., & Klein, A. M. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.05.20.655184 · Cited by 1
An Innate Immune Receptor Toll-1 converts chronic light stress into glial-phagocytosisPreprint
Osaka, J., Ichinose, T., Kanno, M., Hakeda‐Suzuki, S., Suzuki, T., & Sugie, A. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.03.673940 · Cited by 1
Negative Regulation during Bacterial Infection
Stern, A. M., Hsiao, A., & Zhu, J. (2016) · ASM Press eBooks · doi:10.1128/9781555818524.ch26
Porinas e suas ações imunomoduladoras dependentes de TLR2
Nascimento, L. D. O. (2011) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.9.2011.tde-21032013-125043
Design and Development of Recombinant Vaccines with Viral Properties
Lipowsky, G., & Bachmann, M. F. (2011) · Wiley eBooks · doi:10.1002/9781118023648.ch2
Functional Genomics in Shrimp Disease Control
Dhar, A. K., & Robles‐Sikisaka, R. (2012) · doi:10.1002/9781118350041.ch14
An evolutionarily conserved role for autophagy in antiviral defense
Moy, R. H. (2013) · ScholarlyCommons (University of Pennsylvania)
Communication between Pathogens and Eukaryotic Cells
Heesemann, J. (2009) · doi:10.1002/9783527629237.ch5
Databases and computational interaction models of Toll-like receptors
Gong, J. (2010) · Elektronische Hochschulschriften der LMU München (Ludwig-Maximilians-Universität München) · doi:10.5282/edoc.11561
Chadzińska, M., & Idzik, M. (2010)
Jalal, S. (2008) · University Library - University of Saskatchewan (University of Saskatchewan)
Borrego, A. (2009) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.42.2009.tde-07102009-083721
The role of intestinal dendritic cells and the microbiota during oral Salmonella infection
Fernández, M. D. C. G. (2015) · Gothenburg University Publications Electronic Archive (Gothenburg University)
Invertebrate Innate Immune Defenses
Chamy, L. E., Hétru, C., & Hoffmann, J. A. (2014) · ASM Press eBooks · doi:10.1128/9781555816872.ch1
ESPRESSIONE DEI RECETTORI Toll-like IN ORGANI MURINI ADULTI ED EMBRIONALI
Biomediche, S. (2011)
Boltaña, S. (2011) · TDX (Tesis Doctorals en Xarxa)
Innate Immunity in Atopic Dermatitis
Hata, T. R., & Gallo, R. L. (2009) · CRC Press eBooks · doi:10.3109/9781420077995-7
Nucleic Acid Detection in Anti-Viral Responses and Autoimmunity
Brunette, R. L. (2012) · ResearchWorks at the University of Washington (University of Washington)
Enhancement of Protective Immune Responses in Chickens against Marek's Disease Virus
Parvizi, P. (2011) · The Atrium (University of Guelph)
Towards understanding a holobiont: host-microbe interactions in Hydra
Fraune, S. (2009) · MACAU: Open Access Repository of Kiel University (University Library Kiel)
Gazzinelli, R., Fitzgerald, K., & Golenbock, D. (2009) · ASM Press eBooks · doi:10.1128/9781555816650.ch6
Toll-Like Receptor Ligands as Antiviral Agents against Avian Influenza Viruses
Barjesteh, N. (2017) · The Atrium (University of Guelph)
Silent Inflammation – stumme Entzündung
Friedrichsen, H.-P. (2018) · Erfahrungsheilkunde · doi:10.1055/a-0646-9461
Loes, A. N. (2019) · Scholars' Bank (University of Oregon)
Loss of Cysteine Rich domain was critical for evolution of heterodimerization in Toll proteinsPreprint
Ranga, P., Sawanth, S. K., & Mrinal, N. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.01.18.427181
Pinheiro, A. (2021) · Encyclopedia of Life Sciences · doi:10.1002/9780470015902.a0029065
Ageing and the cellular immune response in adult Drosophila melanogaster
Mackenzie, D. K. (2014) · Stirling Online Research Repository (University of Stirling)
Imler, J. (2013) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.718049779.793482844
Faculty Opinions recommendation of Domain architecture evolution of pattern-recognition receptors.
Tomaso, T. D. (2010) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.3047956.2730054
Peterson, J. N., Sivars, K. B., Bianco, A., & Röper, K. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.10.25.465823
Teichmann, S. A., & Hagai, T. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.734763679.793555977
Immunological Discrimination between Self and Nonself
Defaweux, V., & Heinen, E. (2010) · Encyclopedia of Life Sciences · doi:10.1002/9780470015902.a0000899.pub3
de Figueiredo, A. C. (2022) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.41.2022.tde-11072022-152542
Mozhaitseva, K., Tourrain, Z., & Branca, A. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.11.06.564334
Introductory Chapter: Evolution of Toll-Like Receptors
Kumar, V., & Stewart, J. H. (2024) · IntechOpen eBooks · doi:10.5772/intechopen.1004203
Toll-like Receptors: Therapeutic Potential in Life Threatening Diseases- Cardiac Disorders
Singh, S. K. (2024) · Cardiovascular & Haematological Disorders - Drug Targets · doi:10.2174/011871529x348433240915133309
Receptor-based protein binding in the supramolecular network of velvet worm slimePreprint
Hu, Z., Baer, A., Hering, L., Oliveira, I. D. S., Browne, D. C., Guo, X., Perrin, Q. M., Sobota, R. M., Hoon, S. S., Mayer, G., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.10.24.619955
Facing stress and inflammation: From the cell to the planet
Cavaillon, J., & Chaudry, I. H. (2024) · World Journal of Experimental Medicine · doi:10.5493/wjem.v14.i4.96422
Cell death mechanisms in Drosophila: Responses to infectious challenges
Yadav, G. K., Mitra, S., Gupta, R., Mishra, P., & Aggarwal, D. D. (2025) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2025.07.002
Cheng, H., Wang, J., & Ting, W. (2025) · Immunological Investigations · doi:10.1080/08820139.2025.2583276
Genomic approaches to study innate immune response to Salmonella Enteritidis infection in chickens
Chiang, H. (2008) · OakTrust (Texas A&M University Libraries)
Identification of Essential Functions of GRP94 in Metazoan Growth Control and Epithelial Homeostasis
Maynard, J. C. (2009) · DukeSpace (Duke University)
Webb, A. E. (2015) · Dublin City University Open Access Institutional Repository (Dublin City University)
Tait, S., Fratini, F., Boussadia, Z., Gaddini, L., Marra, M., Pera, L. L., Venturini, G., & Ferrante, A. (2025) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2025.111708
Koutsouveli, V., Torres-Oliva, M., Marulanda-Gómez, Á. M., Franke, A., Fuß, J., Schmitz, R. A., Hentschel, U., Reusch, T. B. H., & Pita, L. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1725140
Perez-Sanchez, D., Li, G., Moncrieffe, M. C., Rojo-Cortés, F., Malinovska, K., Sample, E., Maddick, M., Moreira, M., Connolly, E. C., Parsons, A., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.18.706625
Host-pathogens interactions during RSV / S. pneumoniae infection immune response and p53 pathway
Machado, D. B. B. (2017) · theses.fr (ABES) · doi:10.70675/3b4a9038z62abz41fcz8fa8zd0dbd4dcbfe4
Détection et régulation du peptidoglycane lors de la réponse antibactérienne chez la Drosophile
Capo, F. (2017) · theses.fr (ABES) · doi:10.70675/bd5b4c7cz39edz46fdzb3a9zc9d1147a9d2b
Debbabi, S. H. (2018) · theses.fr (ABES) · doi:10.70675/a9e8c6faze8d0z44d4zb97dzcacb09c83ffd
Neuropeptides et néprilysines : rôle dans la mémoire chez la drosophile
Turrel, O. (2017) · theses.fr (ABES) · doi:10.70675/f88da331zc181z4755z95bczb9de3498a523
Les propriétés immunitaires des cellules souches de la pulpe dentaire dans un contexte infectieux
Hamada, A. (2018) · theses.fr (ABES) · doi:10.70675/c8aafcebz816bz4063zb181zf9794e2577b6
Farés, N. (2019) · theses.fr (ABES) · doi:10.70675/eef9404azffadz4212z9948z699104f7c1ab
Trafic, maturation et signalisation proapoptotique de TLR3
Virard, F. (2011) · theses.fr (ABES) · doi:10.70675/7399f411z35f4z4827z8ee6z4c523e081214
The role of TLR7 in Sjögren's syndrome
Wang, Y. (2020) · theses.fr (ABES) · doi:10.70675/69155cbezc742z41b7za0f6z2b1f895a26dd
Jacquemin, G. (2021) · theses.fr (ABES) · doi:10.70675/eb1fecbaz8065z42ebzb918ze92070a1ff72
Zmarlak, N. M. (2021) · theses.fr (ABES) · doi:10.70675/200eea1dzc67ez46bdza893z8bda1f8c2d6f
He, Y.-J., Qi, Y.-H., Wang, C., Jiao, G.-Y., Ye, Z.-X., Lin, L., Mao, Q.-Z., Lu, G., Wang, X.-W., Zhang, C.-X., et al. (2026) · Molecular plant pathology · doi:10.1111/mpp.70259
FcLRR1 Regulates Hyphal Growth and Plant Infection in Fusarium circinatum
Dai, T., Chen, C., Ju, F., Zang, J., Qi, Z., Wang, H., Zhang, X., & Yang, C. (2026) · Journal of Fungi · doi:10.3390/jof12040282
LsToll Gene Mediates Antibacterial Immunity and Developmental Regulation in Loxostege sticticalis
Yan, L., Bai, Y., Zhao, P., Wu, J., Xia, W., Zhang, Y., Wang, X., Zhang, L., & Jiang, H. (2026) · Insects · doi:10.3390/insects17060581
Yakovlev, A. A., Kruglikova, A. A., Tulin, D., & Polev, D. E. (2026) · Journal of Evolutionary Biochemistry and Physiology · doi:10.1134/s0022093026600168
Kumar, S., Bharti, P., Dudeja, P., Sharma, A., & Abnave, P. (2026) · iScience · doi:10.1016/j.isci.2026.116894
Evolutionary Response Patterns of the Rodent TLR Genes to Climatic Factors
Zhao, C., Xia, T., Liu, G., Liu, Z., Ding, X., Dai, S., & Zhang, H. (2026) · Ecology and Evolution · doi:10.1002/ece3.74271
ZBP1 Evolution and Antagonism by Large DNA Viruses
Diallo, M., & Maelfait, J. (2026) · Journal of Molecular Biology · doi:10.1016/j.jmb.2026.170026
Xu, W., Geng, M., Bai, Q., Wang, X., Wang, L., Zhang, Y., Huiyi, F., Zhao, J., Wang, G., & Zhu, T. (2026) · Fishes · doi:10.3390/fishes11100590
Minias, P., Chyb, A., Gaczorek, T. S., & Babik, W. (2026) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2026.1096
Metadata
- Authors
- Leulier, F., & Lemaitre, B.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- ORCID
- Leulier, François
- Venue
- Nature Reviews Genetics
- Published
- 2008-03
- Volume
- 9
- Issue
- 3
- Pages
- 165-178
- ISSN
- 1471-0056 (ISSN-L)
- 1471-0064
- OpenAlex
- W2070793039
- Cited by
- 581
- References
- 131
- Citations by year
- 2026: 20 · 2025: 30 · 2024: 39 · 2023: 28 · 2022: 35 · 2021: 39 · 2020: 32 · 2019: 25 · 2018: 42 · 2017: 31 · 2016: 26 · 2015: 31 · 2014: 30 · 2013: 29 · 2012: 34
- FWCI
- 2.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Reviews Genetics (publishedVersion)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Invertebrate Immune Response Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- Toll-like receptors, immune system evolution, innate immunity, embryonic development, invertebrate immunity, vertebrate immunity, convergent evolution, animal evolution
- MeSH terms
- Animals, Humans, Evolution, Molecular, Toll-Like Receptors
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
