TLR2/TLR4 activation induces Tregs and suppresses intestinal inflammation caused by Fusobacterium nucleatum in vivo
Open accessAbstract
Toll-like receptors (TLRs) 2 and 4 play critical roles in intestinal inflammation caused by Fusobacterium nucleatum (F. nucleatum) infection, but the role of TLR2/TLR4 in regulation of proinflammatory cytokines remains unknown. In this study, through microarray analysis and qRT-PCR, we showed that TLR2/TLR4 are involved in the F. nucleatum-induced inflammatory signaling pathway in Caco-2 cells, C57BL/6 mice and human clinical specimens. In TLR2-/- and TLR4-/- mice, F. nucleatum infection resulted in increased colonization of the bacteria and production of the proinflammatory cytokines IL-8, IL-1β and TNF-α. In addition, the ratio of Foxp3+ CD4+ T cells in the total CD4+ T cells in TLR2-/- and TLR4-/- mice was less than that in wild-type mice, and the ratio in hybrid mice was more than that in knockout mice, which suggested that TLR2/TLR4 mediated the number of Tregs. Furthermore, it was observed that inflammatory cytokine levels were reduced in TLR2-/- mice after Treg transfer. Thus, these data indicate that TLR2/TLR4 regulate F. nucleatum-induced inflammatory cytokines through Tregs in vivo.
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Toxins in the brain can specifically recognize and combine with TLR4, activate microglia and eventually lead to neuroinflammation.
“Toxins in the brain can specifically recognize and combine with TLR4, activate the microglia and eventually lead to neuroinflammation (Jia et al. 2017).”
From Therapeutic effect of GLP-1 engineered strain on mice model of Alzheimer’s disease and Parkinson’s disease (2020) · cites this paper as Jia et al. 2017
Increase in Fusobacterium nucleatum promotes the production of inflammatory factors IL-8, IL-1β and TNF-α, ultimately leading to intestinal epithelial inflammation.
“As we know, an increase in Fusobacterium nucleatum (F. nucleatum) promotes the production of the inflammatory factors IL-8, IL-1β and TNF-α, ultimately leads to intestinal epithelial inflammation (Jia et al. 2017).”
From Therapeutic effect of GLP-1 engineered strain on mice model of Alzheimer’s disease and Parkinson’s disease (2020) · cites this paper as Jia et al. 2017
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- Authors
- Jia, Y.-P., Wang, K., Zhang, Z.-J., Tong, Y.-N., Han, D., Hu, C.-Y., Li, Q., Xiang, Y., Mao, X.-H., & Tang, B.
- Affiliations
- Army Medical University (CN)
- Corresponding author
- Tang, Bin
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2017-10-09
- Volume
- 12
- Issue
- 10
- Pages
- e0186179
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC5633168
- OpenAlex
- W2760979956
- Cited by
- 65
- References
- 27
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 9 · 2023: 7 · 2022: 11 · 2021: 11 · 2020: 8 · 2019: 5 · 2018: 2 · 2017: 1
- FWCI
- 1.98
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (81501796)
- the project of medical science and technology for training youth scholars of PLA (14QNP054)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- TLR2, TLR4, Fusobacterium nucleatum, regulatory T cells, Foxp3, intestinal inflammation, inflammatory cytokines, interleukin-8, IL-1β, TNF-α, Treg transfer, gut microbiota, Caco-2 cells, TLR2 knockout mice, TLR4 knockout mice
- MeSH terms
- Adult, Animals, Female, Fusobacterium Infections, Humans, Inflammation, Intestines, Male, Middle Aged, Signal Transduction, Fusobacterium nucleatum, Mice, Knockout, Caco-2 Cells, Microarray Analysis, T-Lymphocytes, Regulatory, Toll-Like Receptor 2, Toll-Like Receptor 4, Mice
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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