Linking genetic variation in human Toll-like receptor 5 genes to the gut microbiome's potential to cause inflammation
Open accessAbstract
Immunodeficiencies can lead to alterations of the gut microbiome that render it pathogenic and capable of transmitting disease to naïve hosts. Here, we review the role of Toll-like receptor (TLR) 5, the innate receptor for bacterial flagellin, in immune responses to the normal gut microbiota with a focus its role on adaptive immunity. Loss of TLR5 has profound effects on the microbiota that include greater temporal instability of major lineages and upregulation of flagellar motility genes that may be linked to the reduced levels of anti-flagellin antibodies in the TLR5(-/-) host. A variety of human TLR5 gene alleles exist that also associated with inflammatory conditions and may do so via effects on the gut microbiome and altered host-microbial crosstalk.
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Expression and activation of TLR5 on IECs regulates the composition and localization of microbiota and prevents disease associated intestinal inflammation.
“It was demonstrated in numerous reports from Dr Gewirtz’s group that expression and activation of TLR5 on IECs regulates the composition and localization of microbiota and prevents disease associated intestinal inflammation.165, 166, 167, 168”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [167]
Variations in TLR5 genes are associated with a number of inflammatory diseases.
“Interestingly, variations in TLR5 genes are associated with a number of inflammatory diseases (Leifer et al., 2014).”
From Viral Infections, the Microbiome, and Probiotics (2021) · cites this paper as Leifer et al., 2014
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- Authors
- Leifer, C. A., McConkey, C., Li, S., Chassaing, B., Gewirtz, A. T., & Ley, R. E.
- Affiliations
- Cornell University (US)
- Georgia State University (US)
- Venue
- Immunology Letters
- Publisher
- Elsevier BV
- Published
- 2014-12
- Volume
- 162
- Issue
- 2
- Pages
- 3-9
- ISSN
- 0165-2478 (ISSN-L)
- PMC
- PMC4259828
- OpenAlex
- W2059804687
- Cited by
- 34
- References
- 74
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 1 · 2022: 1 · 2021: 4 · 2020: 1 · 2019: 3 · 2018: 3 · 2017: 3 · 2016: 6 · 2015: 2 · 2014: 1
- FWCI
- 0.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Immunology Letters (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI076588, R03AI097671)
- 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
- TLR5, flagellin, gut microbiota, genetic variation, inflammation, adaptive immunity, anti-flagellin antibodies, host-microbe crosstalk, immunodeficiency
- MeSH terms
- Animals, Antibody Formation, Flagellin, Humans, Immunity, Innate, Inflammation, Intestinal Mucosa, Genetic Variation, Gene Expression Regulation, Bacterial, Mice, Knockout, Genetic Predisposition to Disease, Toll-Like Receptor 5, Mice, Adaptive Immunity, Microbiota
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 ›
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