Cited by 4,251Immune Response and InflammationGut microbiota and healthGastrointestinal motility and disorders

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Recognition of Commensal Microflora by Toll-Like Receptors Is Required for Intestinal Homeostasis

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Rakoff-Nahoum, Seth, Paglino, Justin, Eslami-Varzaneh, Fatima, Edberg, Stephen, Medzhitov, Ruslan·2004·Cell

DOI 10.1016/j.cell.2004.07.002

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Abstract

Toll-like receptors (TLRs) play a crucial role in host defense against microbial infection. The microbial ligands recognized by TLRs are not unique to pathogens, however, and are produced by both pathogenic and commensal microorganisms. It is thought that an inflammatory response to commensal bacteria is avoided due to sequestration of microflora by surface epithelia. Here, we show that commensal bacteria are recognized by TLRs under normal steady-state conditions, and this interaction plays a crucial role in the maintenance of intestinal epithelial homeostasis. Furthermore, we find that activation of TLRs by commensal microflora is critical for the protection against gut injury and associated mortality. These findings reveal a novel function of TLRs-control of intestinal epithelial homeostasis and protection from injury-and provide a new perspective on the evolution of host-microbial interactions.

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Toll-Like Receptors
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Authors: Rakoff-Nahoum, S., Paglino, J., Eslami-Varzaneh, F., Edberg, S., & Medzhitov, R.
Affiliations: Howard Hughes Medical Institute (US)
Yale University (US)
Corresponding author: Medzhitov, Ruslan
ORCID: Rakoff-Nahoum, Seth
Medzhitov, Ruslan
Venue: Cell
Publisher: Elsevier BV
Published: 2004-07
Volume: 118
Issue: 2
Pages: 229-241
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2004.07.002
OpenAlex: W2083089709
Cited by: 4,251
References: 63
Citations by year: 2026: 110 · 2025: 105 · 2024: 115 · 2023: 156 · 2022: 201 · 2021: 204 · 2020: 206 · 2019: 178 · 2018: 200 · 2017: 179 · 2016: 211 · 2015: 199 · 2014: 234 · 2013: 243 · 2012: 234
FWCI: 64.13
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 3303 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of General Medical Sciences (GM07205, T32GM007205)
National Institute of Allergy and Infectious Diseases (AI-46688)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords: Toll-like receptors, commensal bacteria, intestinal epithelial homeostasis, host-microbe interactions, intestinal injury, microbial ligands, innate immunity, intestinal inflammation, host defense
MeSH terms: Animals, Antigens, Differentiation, Bacteria, Cells, Cultured, Chemotaxis, Leukocyte, Colon, Female, Heat-Shock Proteins, Homeostasis, Immunity, Immunity, Innate, Intestinal Mucosa, Ligands, Male, Membrane Glycoproteins, Receptors, Cell Surface, Receptors, Immunologic, Symbiosis, Cytokines, Mice, Knockout, Adaptor Proteins, Signal Transducing, Toll-Like Receptors, Mice, Myeloid Differentiation Factor 88

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Recognition of Commensal Microflora by Toll-Like Receptors Is Required for Intestinal Homeostasis

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