The DOI matches its Crossref record.
Cutting Edge: Bacterial Flagellin Activates Basolaterally Expressed TLR5 to Induce Epithelial Proinflammatory Gene Expression
Open accessAbstract
Flagellin, the structural component of bacterial flagella, is secreted by pathogenic and commensal bacteria. Flagellin activates proinflammatory gene expression in intestinal epithelia. However, only flagellin that contacts basolateral epithelial surfaces is proinflammatory; apical flagellin has no effect. Pathogenic Salmonella, but not commensal Escherichia coli, translocate flagellin across epithelia, thus activating epithelial proinflammatory gene expression. Investigating how epithelia detect flagellin revealed that cell surface expression of Toll-like receptor 5 (TLR5) conferred NF-κB gene expression in response to flagellin. The response depended on both extracellular leucine-rich repeats and intracellular Toll/IL-1R homology region of TLR5 as well as the adaptor protein MyD88. Furthermore, immunolocalization and cell surface-selective biotinylation revealed that TLR5 is expressed exclusively on the basolateral surface of intestinal epithelia, thus providing a molecular basis for the polarity of this innate immune response. Thus, detection of flagellin by basolateral TLR5 mediates epithelial-driven inflammatory responses to Salmonella.
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.
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
Cited by
Takeda, K., Kaisho, T., & Akira, S. (2003) · Annual Review of Immunology · doi:10.1146/annurev.immunol.21.120601.141126 · Cited by 6,143
Toll-like receptors and innate immunity
Medzhitov, R. (2001) · Nature Reviews Immunology · doi:10.1038/35100529 · Cited by 4,308
Recognition of Commensal Microflora by Toll-Like Receptors Is Required for Intestinal Homeostasis
Rakoff-Nahoum, S., Paglino, J., Eslami-Varzaneh, F., Edberg, S., & Medzhitov, R. (2004) · Cell · doi:10.1016/j.cell.2004.07.002 · Cited by 4,251
Toll-like receptors in innate immunity
Takeda, K. (2004) · International Immunology · doi:10.1093/intimm/dxh186 · Cited by 3,328
The gut flora as a forgotten organ
O'Hara, A. M., & Shanahan, F. (2006) · The EMBO Reports · doi:10.1038/sj.embor.7400731 · Cited by 2,791
Abraham, C., & Cho, J. H. (2009) · New England Journal of Medicine · doi:10.1056/nejmra0804647 · Cited by 2,712
The two NF-κB activation pathways and their role in innate and adaptive immunity
Bonizzi, G., & Karin, M. (2004) · Trends in Immunology · doi:10.1016/j.it.2004.03.008 · Cited by 2,535
Toll-like Receptors and the Control of Immunity
Fitzgerald, K. A., & Kagan, J. C. (2020) · Cell · doi:10.1016/j.cell.2020.02.041 · Cited by 2,168
Innate Immune Pattern Recognition: A Cell Biological Perspective
Brubaker, S. W., Bonham, K. S., Zanoni, I., & Kagan, J. C. (2015) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032414-112240 · Cited by 1,475
Mucin dynamics and enteric pathogens
McGuckin, M. A., Lindén, S. K., Sutton, P., & Florin, T. H. (2011) · Nature Reviews Microbiology · doi:10.1038/nrmicro2538 · Cited by 1,428
Abreu, M. T. (2010) · Nature Reviews Immunology · doi:10.1038/nri2707 · Cited by 1,288
Epithelial-cell recognition of commensal bacteria and maintenance of immune homeostasis in the gut
Artis, D. (2008) · Nature reviews. Immunology · doi:10.1038/nri2316 · Cited by 1,136
Barthel, M., Hapfelmeier, S., Quintanilla-Martínez, L., Kremer, M., Rohde, M., Hogardt, M., Pfeffer, K., Rüssmann, H., & Hardt, W.-D. (2003) · Infection and Immunity · doi:10.1128/iai.71.5.2839-2858.2003 · Cited by 1,020
Host interactions of probiotic bacterial surface molecules: comparison with commensals and pathogens
Lebeer, S., Vanderleyden, J., & De Keersmaecker, S. C. J. (2010) · Nature Reviews Microbiology · doi:10.1038/nrmicro2297 · Cited by 1,062
Ubeda, C., Taur, Y., Jenq, R. R., Equinda, M. J., Son, T., Samstein, M., Viale, A., Socci, N. D., van den Brink, M. R. M., Kamboj, M., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci43918 · Cited by 943
Interaction between the gut microbiome and mucosal immune system
Shi, N., Li, N., Duan, X., & Niu, H. (2017) · Military Medical Research · doi:10.1186/s40779-017-0122-9 · Cited by 940
Bacterial flagellin is a dominant antigen in Crohn disease
Lodes, M. J., Cong, Y., Elson, C. O., Mohamath, R., Landers, C. J., Targan, S. R., Fort, M., & Hershberg, R. M. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200420295 · Cited by 802
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
Self-citationLiévin-Le Moal, V., & Servin, A. L. (2006) · Clinical Microbiology Reviews · doi:10.1128/cmr.19.2.315-337.2006 · Cited by 568
Oh, J. Z., Ravindran, R., Chassaing, B., Carvalho, F. A., Maddur, M. S., Bower, M., Hakimpour, P., Gill, K. P., Nakaya, H. I., Yarovinsky, F., et al. (2014) · Immunity · doi:10.1016/j.immuni.2014.08.009 · Cited by 541
Self-citationImmune Responses to the Microbiota at the Intestinal Mucosal Surface
Duerkop, B. A., Vaishnava, S., & Hooper, L. V. (2009) · Immunity · doi:10.1016/j.immuni.2009.08.009 · Cited by 424
Flagellin as an Adjuvant: Cellular Mechanisms and Potential
Mizel, S. B., & Bates, J. T. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1002156 · Cited by 399
“The induction of cytokines and chemokines is a key first step in the adjuvant effect of flagellin (4, 45) and probably involves a number of flagellin-responsive cell types (e.”
BackgroundPrice, A. E., Shamardani, K., Lugo, K. A., Deguine, J., Roberts, A. W., Lee, B. L., & Barton, G. M. (2018) · Immunity · doi:10.1016/j.immuni.2018.07.016 · Cited by 379
Chassaing, B., Ley, R. E., & Gewirtz, A. T. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.08.033 · Cited by 326
Microbiota-mediated inflammation and antimicrobial defense in the intestine
Caballero, S., & Pamer, E. G. (2015) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120238 · Cited by 238
Kinnebrew, M. A., Ubeda, C., Zenewicz, L. A., Smith, N., Flavell, R. A., & Pamer, E. G. (2010) · The Journal of Infectious Diseases · doi:10.1086/650203 · Cited by 236
Rhee, S. H., Im, E., Riegler, M., Kokkotou, E., O'Brien, M., & Pothoulakis, C. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0502174102 · Cited by 229
Toll-Like Receptors: Regulators of the Immune Response in the Human Gut
Hug, H., Mohajeri, M., & La Fata, G. (2018) · Nutrients · doi:10.3390/nu10020203 · Cited by 217
Life in the inflamed intestine, Salmonella style
Santos, R. L., Raffatellu, M., Bevins, C. L., Adams, L. G., Tükel, Ç., Tsolis, R. M., & Bäumler, A. J. (2009) · Trends in Microbiology · doi:10.1016/j.tim.2009.08.008 · Cited by 197
From bench to bedside: stealth of enteroinvasive pathogens
Tsolis, R. M., Young, G. M., Solnick, J. V., & Bäumler, A. J. (2008) · Nature Reviews Microbiology · doi:10.1038/nrmicro2012 · Cited by 141
Evolution of Salmonella-Host Cell Interactions through a Dynamic Bacterial Genome
Ilyas, B., Tsai, C. N., & Coombes, B. K. (2017) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2017.00428 · Cited by 128
Capsule-mediated immune evasion: a new hypothesis explaining aspects of typhoid fever pathogenesis
Raffatellu, M., Chessa, D., Wilson, R. P., Tükel, C., Akçelik, M., & Bäumler, A. J. (2006) · Infection and Immunity · doi:10.1128/iai.74.1.19-27.2006 · Cited by 123
How flagellin and toll-like receptor 5 contribute to enteric infection
Steiner, T. S. (2007) · Infection and Immunity · doi:10.1128/iai.01506-06 · Cited by 97
López-Boado, Y. S., Espinola, M., Bahr, S., & Belaaouaj, A. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.1.509 · Cited by 92
Rhee, S. H., Keates, A. C., Moyer, M. P., & Pothoulakis, C. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m400967200 · Cited by 81
Carvalho, F. A., Aitken, J. D., Gewirtz, A. T., & Vijay-Kumar, M. (2011) · Mucosal Immunology · doi:10.1038/mi.2010.57 · Cited by 80
Self-citationLauté-Caly, D. L., Raftis, E. J., Cowie, P., Hennessy, E., Holt, A., Panzica, D. A., Sparre, C., Minter, B., Stroobach, E., & Mulder, I. E. (2019) · Scientific Reports · doi:10.1038/s41598-018-36926-8 · Cited by 67
UNC93B1 is essential for the plasma membrane localization and signaling of Toll-like receptor 5
Huh, J.-W., Shibata, T., Hwang, M., Kwon, E.-H., Jang, M. S., Fukui, R., Kanno, A., Jung, D.-J., Jang, M. H., Miyake, K., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1322838111 · Cited by 65
Fedirko, V., Tran, H. Q., Gewirtz, A. T., Stepien, M., Trichopoulou, A., Aleksandrova, K., Olsen, A., Tjønneland, A., Overvad, K., Carbonnel, F., et al. (2017) · BMC Medicine · doi:10.1186/s12916-017-0830-8 · Cited by 50
Self-citationLeifer, C. A., McConkey, C., Li, S., Chassaing, B., Gewirtz, A. T., & Ley, R. E. (2014) · Immunology Letters · doi:10.1016/j.imlet.2014.07.017 · Cited by 34
Self-citationLopetuso, L. R., Jia, R., Wang, X.-M., Jia, L.-G., Petito, V., Goodman, W. A., Meddings, J. B., Cominelli, F., Reuter, B. K., & Pizarro, T. T. (2017) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000001035 · Cited by 28
Uchida, M., Oyanagi, E., Kawanishi, N., Iemitsu, M., Miyachi, M., Kremenik, M. J., Onodera, S., & Yano, H. (2014) · Immunology Letters · doi:10.1016/j.imlet.2013.12.021 · Cited by 18
Salmonella: Invasion, Evasion & Persistence
Chami, B., & Bao, S. (2012) · Salmonella - Distribution, Adaptation, Control Measures and Molecular Technologies · doi:10.5772/30443 · Cited by 3
Metadata
- Authors
- Gewirtz, A. T., Navas, T. A., Lyons, S., Godowski, P. J., & Madara, J. L.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2001-08
- Volume
- 167
- Issue
- 4
- Pages
- 1882-1885
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2130501069
- Cited by
- 1,346
- References
- 0
- FWCI
- 18.17
- Type
- journal article
- Language
- en
- Open access
- bronze
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
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
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.
