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Epithelial-cell recognition of commensal bacteria and maintenance of immune homeostasis in the gut
Abstract
Mucosal surfaces such as the intestinal tract are continuously exposed to both potential pathogens and beneficial commensal microorganisms. This creates a requirement for a homeostatic balance between tolerance and immunity that represents a unique regulatory challenge to the mucosal immune system. Recent findings suggest that intestinal epithelial cells, although once considered a simple physical barrier, are a crucial cell lineage for maintaining intestinal immune homeostasis. This Review discusses recent findings that identify a cardinal role for epithelial cells in sampling the intestinal microenvironment, discriminating pathogenic and commensal microorganisms and influencing the function of antigen-presenting cells and lymphocytes.
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“The host-microbiota relationship has been defined as the synergistic effect of microbial metabolites on host immunity, health and disease, energy metabolism, and cellular communication.59, 60, 61, 62, 63,64”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [64]
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The Effects of Airway Microbiome on Corticosteroid Responsiveness in Asthma
Goleva, E., Jackson, L. P., Harris, J. K., Robertson, C. E., Sutherland, E. R., Hall, C. F., Good, J. T., Gelfand, E. W., Martin, R. J., & Leung, D. Y. M. (2013) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201304-0775oc · Cited by 363
“Recent literature suggests that commensal microbiota maintains and shapes normal mucosal immunity in the gut (44, 45).”
BackgroundAntibiotics, microbiota, and immune defense
Úbeda, C., & Pamer, E. G. (2012) · Trends in Immunology · doi:10.1016/j.it.2012.05.003 · Cited by 369
Taylor, B. C., Zaph, C., Troy, A. E., Du, Y., Guild, K. J., Comeau, M. R., & Artis, D. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20081499 · Cited by 340
Nakajima, A., Vogelzang, A., Maruya, M., Miyajima, M., Murata, M., Son, A., Kuwahara, T., Tsuruyama, T., Yamada, S., Matsuura, M., et al. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20180427 · Cited by 351
“The gut microbiota is essential for host physiology, as it regulates the metabolism, epithelial barrier integrity, and immune system development and function (Bäckhed et al., 2005; Artis, 2008; Belkaid and Hand, 2014).”
BackgroundTurroni, F., Ventura, M., Buttó, L. F., Duranti, S., O’Toole, P. W., Motherway, M. O., & van Sinderen, D. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-013-1318-0 · Cited by 336
“PRRs encompass a long list of receptors such as the Toll-like receptors (TLRs), NOD-like receptors (NRLs), and C-type lectin receptors (CLRs) [154].”
BackgroundBreast milk, microbiota, and intestinal immune homeostasis
Walker, W. A., & Iyengar, S. R. (2014) · Pediatric Research · doi:10.1038/pr.2014.160 · Cited by 349
“In a review in Nature Reviews Immunology (19), Artis underscores the important contributions of commensal bacteria to the intestinal epithelial cell barrier (Figure 2).”
InfluentialThe microbiome and regulation of mucosal immunity
McDermott, A. J., & Huffnagle, G. B. (2013) · Immunology · doi:10.1111/imm.12231 · Cited by 351
Leslie, J. L., Huang, S., Opp, J. S., Nagy, M. S., Kobayashi, M., Young, V. B., & Spence, J. R. (2014) · Infection and Immunity · doi:10.1128/iai.02561-14 · Cited by 330
“The gastrointestinal epithelium is an interface between the host and the environment and is crucial for many aspects of health, including nutrient absorption, maintenance of immune homeostasis, and forming a selective barrier against antigens (38, 39).”
BackgroundBiological Gene Delivery Vehicles: Beyond Viral Vectors
Seow, Y., & Wood, M. J. A. (2009) · Molecular Therapy · doi:10.1038/mt.2009.41 · Cited by 331
Gerassy-Vainberg, S., Blatt, A., Danin‐Poleg, Y., Gershovich, K., Sabo, E., Nevelsky, A., Daniel, S., Dahan, A., Ziv, O., Dheer, R., et al. (2017) · Gut · doi:10.1136/gutjnl-2017-313789 · Cited by 331
Treatment, promotion, commotion: antibiotic alternatives in food-producing animals
Allen, H. K., Levine, U. Y., Looft, T. P., Bandrick, M., & Casey, T. A. (2013) · Trends in Microbiology · doi:10.1016/j.tim.2012.11.001 · Cited by 337
Chu, V. T., Beller, A. V., Rausch, S., Strandmark, J., Zänker, M., Arbach, O., Kruglov, A., & Berek, C. (2014) · Immunity · doi:10.1016/j.immuni.2014.02.014 · Cited by 323
Genome-Wide RNAi Screen Identifies Genes Involved in Intestinal Pathogenic Bacterial Infection
Cronin, S. J. F., Nehme, N. T., Schirmeier, S., Liégeois, S., Pospisilik, J. A., Schramek, D., Leibbrandt, A., Simoes, R. D. M., Gruber, S., Puc, U., et al. (2009) · Science · doi:10.1126/science.1173164 · Cited by 321
Intestinal Epithelial Autophagy Is Essential for Host Defense against Invasive Bacteria
Benjamin, J. L., Sumpter, R., Levine, B., & Hooper, L. V. (2013) · Cell Host & Microbe · doi:10.1016/j.chom.2013.05.004 · Cited by 312
“In addition to secreting antimicrobial proteins, the intestinal epithelium also orchestrates adaptive immune responses to intestinal bacteria through the secretion of cytokines and other factors (Artis, 2008).”
Interactions Between the Gastrointestinal Microbiome and Clostridium difficile
Theriot, C. M., & Young, V. B. (2015) · Annual Review of Microbiology · doi:10.1146/annurev-micro-091014-104115 · Cited by 320
“They confer colonization resistance, shape the host immune response, and participate in key metabolic transformations (5, 63, 121).”
BackgroundRole of β7 Integrins in Intestinal Lymphocyte Homing and Retention
Gorfu, G., Rivera-Nieves, J., & Ley, K. (2009) · Current Molecular Medicine · doi:10.2174/156652409789105525 · Cited by 292
Probiotics: Properties, Examples, and Specific ApplicationsPreprint
Behnsen, J., Deriu, E., Sassone‐Corsi, M., & Raffatellu, M. (2013) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a010074 · Cited by 305
“This balance between tolerance and immunity, when disrupted, can lead to the development of a number of intestinal pathologies including inflammatory bowel disease (IBD) and intestinal cancer (Karin et al. 2006; Artis 2008).”
BackgroundIntestinal epithelial cells: At the interface of the microbiota and mucosal immunity
Soderholm, A. T., & Pedicord, V. A. (2019) · Immunology · doi:10.1111/imm.13117 · Cited by 281
Sengupta, R., Altermann, E., Anderson, R. C., McNabb, W. C., Moughan, P. J., & Roy, N. C. (2013) · Mediators of Inflammation · doi:10.1155/2013/237921 · Cited by 301
“Bacterial surfaces exhibit characteristic features known as microbe-associated molecular patterns (MAMP), which are usually cell wall components, such as LPS, PG, LTA, and WTA, but can also be lipids, lipoproteins, proteins, and nucleic acids [142, 143].”
BackgroundVereecke, L., Sze, M., Guire, C. M., Rogiers, B., Chu, Y., Schmidt‐Supprian, M., Pasparakis, M., Beyaert, R., & Loo, G. (2010) · The Journal of Experimental Medicine · doi:10.1084/jem.20092474 · Cited by 283
“There is multiple evidence that epithelial NF-B preserves the integrity of the gut epithelial barrier and maintains immune homeostasis in the gut (Ben-Neriah and Schmidt-Supprian, 2007; Artis, 2008; Pasparakis, 2008).”
InfluentialMileti, E., Matteoli, G., Iliev, I. D., & Rescigno, M. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007056 · Cited by 272
“B ac ill u s su b ti lis P B 6 R at s: T N B S Y e s R e d u ce d co lo n ic d am ag e , re d u ce d se ru m in fl am m at o ry cy to ki n e s [5 2 ]”
BackgroundInfluentialAlcohol, inflammation, and gut-liver-brain interactions in tissue damage and disease development
Wang, H. J. (2010) · World Journal of Gastroenterology · doi:10.3748/wjg.v16.i11.1304 · Cited by 288
The Role of Probiotics and Prebiotics in Inducing Gut Immunity
Vieira, A. T., Teixeira, M. M., & Martins, F. S. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00445 · Cited by 284
IL‐10 and IL‐10 receptor defects in humans
Glocker, E., Kotlarz, D., Klein, C., Shah, N., & Grimbacher, B. (2011) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2011.06339.x · Cited by 270
Glutamine and intestinal barrier function
Wang, B., Wu, G., Zhou, Z., Dai, Z., Sun, Y., Ji, Y. S., Li, W., Wang, W., Liu, C., Han, F. X., et al. (2014) · Amino Acids · doi:10.1007/s00726-014-1773-4 · Cited by 267
The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria
Hansson, G. C., & Johansson, M. (2010) · Gut Microbes · doi:10.4161/gmic.1.1.10470 · Cited by 264
“In fact, intestinal mucus is often missing in illustrations depicting gut protection.(6) One reason for this may be our relatively poor understanding of how the mucus is organized and its molecular nature.”
BackgroundProbiotics and chronic kidney disease
Koppe, L., Mafra, D., & Fouque, D. P. (2015) · Kidney International · doi:10.1038/ki.2015.255 · Cited by 266
Gut-Brain Psychology: Rethinking Psychology From the Microbiota–Gut–Brain Axis
Liang, S., Wu, X., & Jin, F. (2018) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2018.00033 · Cited by 279
“Many PRRs, such as toll-like receptors (TLRs) and nucleotide oligomerization domain-like receptors (NLRs), are expressed in enterocytes; they recognize microbiota material and stimulate a series of immune responses to eliminate or inactivate the pathogen, but tolerate the commensal and harmless material (Artis, 2008;…”
BackgroundLevine, M. M. (2010) · BMC Biology · doi:10.1186/1741-7007-8-129 · Cited by 265
Wei, M., Shinkura, R., Doi, Y., Maruya, M., Fagarasan, S., & Honjo, T. (2011) · Nature Immunology · doi:10.1038/ni.1991 · Cited by 262
“1991" language="eng" relation="no"> The intestinal mucosal surface is the front line of host defense against various pathogens, food antigens and commensal bacteria in the gu”
BackgroundImmunomodulation by radiotherapy in tumour control and normal tissue toxicity
Cytlak, U., Dyer, D. P., Honeychurch, J., Williams, K. J., Travis, M. A., & Illidge, T. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-021-00568-1 · Cited by 277
Do symbiotic bacteria subvert host immunity?
Hooper, L. V. (2009) · Nature Reviews Microbiology · doi:10.1038/nrmicro2114 · Cited by 269
“Limiting immune activation Intestinal epithelial cells express pattern recognition receptors, including TLRs and members of the Nod famil”
BackgroundThe intestinal barrier function and its involvement in digestive disease
Salvo‐Romero, E., Alonso, C., Pardo‐Camacho, C., Casado‐Bedmar, M., & Vicario, M. (2015) · Revista Española de Enfermedades Digestivas · doi:10.17235/reed.2015.3846/2015 · Cited by 280
Metadata
- Authors
- Artis, D.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Artis, David
- ORCID
- Artis, David
- Venue
- Nature reviews. Immunology
- Published
- 2008-06
- Volume
- 8
- Issue
- 6
- Pages
- 411-420
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- OpenAlex
- W2025114863
- Cited by
- 1,136
- References
- 167
- Citations by year
- 2026: 27 · 2025: 33 · 2024: 38 · 2023: 55 · 2022: 61 · 2021: 54 · 2020: 51 · 2019: 52 · 2018: 60 · 2017: 56 · 2016: 58 · 2015: 63 · 2014: 92 · 2013: 85 · 2012: 81
- FWCI
- 6.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (T32CA009140, T32-CA09140-30)
- National Institute of General Medical Sciences (F31-GM82187, F31GM082187)
- National Institute of Allergy and Infectious Diseases (AI74878, T32AI007532, R01AI074878, F32-AI72943, F32AI072943, R01AI061570, AI 61570)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- intestinal epithelial cells, commensal bacteria, immune homeostasis, mucosal immunity, host-microbe interactions, epithelial barrier function, antigen presentation, lymphocytes, pathogen discrimination, gut microbiota
- MeSH terms
- Animals, Bacteria, Gastric Mucosa, Homeostasis, Humans, Intestinal Mucosa
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