Evidence map›Paper›PMID 37871107›Full record

ArticlePLoS pathogens2023

Periodontitis promotes bacterial extracellular vesicle-induced neuroinflammation in the brain and trigeminal ganglion.

Jae Yeong Ha, Jiwon Seok, Suk-Jeong Kim, Hye-Jin Jung, Ka-Young Ryu, Michiko Nakamura, Il-Sung Jang, Su-Hyung Hong, Youngkyun Lee, Heon-Jin Lee

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
4.6field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.

  1. Pooled it
  2. Virulence · 2026
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  8. Journal of oral microbiology · 2026
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  10. Frontiers in microbiology · 2026
    Review
  11. Peptide PN5 fromACS omega · 2025
    Article
  12. Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. Therapeutic Potential of Extracellular Vesicles in Oral Inflammation.International journal of molecular sciences · 2025
    Review
  18. Peripheral proteinopathy in neurodegenerative diseases.Translational neurodegeneration · 2025
    Review
  19. Review
  20. From Global to Nano: A Geographical Perspective ofPathogens (Basel, Switzerland) · 2024
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Jae Yeong HaDepartment of Microbiology and Immunology, School of Dentistry, Kyungpook National University, Daegu, Korea.
Jiwon SeokDepartment of Biochemistry, School of Dentistry, Kyungpook National University, Daegu, Korea.
Suk-Jeong KimDepartment of Microbiology and Immunology, School of Dentistry, Kyungpook National University, Daegu, Korea.
Hye-Jin JungDepartment of Biochemistry, School of Dentistry, Kyungpook National University, Daegu, Korea.
Ka-Young RyuCraniofacial Nerve-Bone Network Research Center, Kyungpook National University, Daegu, Korea.
Michiko NakamuraDepartment of Pharmacology, School of Dentistry, Kyungpook National University, Daegu, Korea.
Il-Sung JangDepartment of Pharmacology, School of Dentistry, Kyungpook National University, Daegu, Korea.
Su-Hyung HongDepartment of Microbiology and Immunology, School of Dentistry, Kyungpook National University, Daegu, Korea.
Youngkyun LeeCraniofacial Nerve-Bone Network Research Center, Kyungpook National University, Daegu, Korea.
Heon-Jin LeeDepartment of Microbiology and Immunology, School of Dentistry, Kyungpook National University, Daegu, Korea.ORCID 0000-0002-1911-5014
Kyungpook National University · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Gram-negative bacteria derived extracellular vesicles (EVs), also known as outer membrane vesicles, have attracted significant attention due to their pathogenic roles in various inflammatory diseases. We recently demonstrated that EVs secreted by the periodontopathogen Aggregatibacter actinomycetemcomitans (Aa) can cross the blood-brain barrier (BBB) and that their extracellular RNA cargo can promote the secretion of proinflammatory cytokines, such as IL-6 and TNF-α, in the brain. To gain more insight into the relationship between periodontal disease (PD) and neuroinflammatory diseases, we investigated the effect of Aa EVs in a mouse model of ligature-induced PD. When EVs were administered through intragingival injection or EV-soaked gel, proinflammatory cytokines were strongly induced in the brains of PD mice. The use of TLR (Toll-like receptor)-reporter cell lines and MyD88 knockout mice confirmed that the increased release of cytokines was triggered by Aa EVs via TLR4 and TLR8 signaling pathways and their downstream MyD88 pathway. Furthermore, the injection of EVs through the epidermis and gingiva resulted in the direct retrograde transfer of Aa EVs from axon terminals to the cell bodies of trigeminal ganglion (TG) neurons and the subsequent activation of TG neurons. We also found that the Aa EVs changed the action potential of TG neurons. These findings suggest that EVs derived from periodontopathogens such as Aa might be involved in pathogenic pathways for neuroinflammatory diseases, neuropathic pain, and other systemic inflammatory symptoms as a comorbidity of periodontitis.

Indexed as

Extracellular VesiclesPeriodontal DiseasesPeriodontitisAnimalsBlood-Brain BarrierCytokinesMiceMice, KnockoutMyeloid Differentiation Factor 88Neuroinflammatory DiseasesTrigeminal GanglionCytokinesMyeloid Differentiation Factor 88

Identifiers

PMID37871107
PMCPMC10621956
OpenAlexW4387873266

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.