Evidence map›Paper›PMID 23906644›Full record

Trial reportJournal of leukocyte biology2013

Human TLR8 is activated upon recognition of Borrelia burgdorferi RNA in the phagosome of human monocytes.

Jorge L Cervantes, Carson J La Vake, Bennett Weinerman, Stephanie Luu, Caitlin O'Connell, Paulo H Verardi, Juan C Salazar

Open access · greenAbstract readClinical TrialMulticenter Study
In one paragraph

Trial report in Journal of leukocyte biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
6.0field-weighted citation impact, top 3% 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

53 citing papers in PubMed, 85 citations in OpenAlex.

  1. Article
  2. Lyme borreliosis.Nature reviews. Disease primers · 2026
    Review
  3. Type I interferon signaling promotes early innate control ofbioRxiv : the preprint server for biology · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Human macrophage polarization in the response toCurrent research in microbial sciences · 2021
    Article
  13. Article
  14. Article
  15. Article
  16. Stimulated Immune Response by TruCultureFrontiers in cellular and infection microbiology · 2021
    Observational
  17. Review
  18. Immune Response toCurrent issues in molecular biology · 2021
    Article
  19. Bioinformatics-Based Study to Investigate Potential Differentially Expressed Genes and miRNAs in Pediatric Sepsis.Medical science monitor : international medical journal of experimental and clinical research · 2020
    Article
  20. RNA Sensing ofVaccines · 2020
    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

7 authors at 3 institutions in 1 country.

Jorge L Cervantes1.Connecticut Children's Medical Center, Division of Infectious Diseases and Immunology, 282 Washington St., Hartford, CT 06106. jsalazar@nso1.uchc.edu.
Carson J La Vake
Bennett Weinerman
Stephanie Luu
Caitlin O'Connell
Paulo H Verardi
Juan C Salazar
UConn Health · USUniversity of Connecticut · USConnecticut Children's Medical Center · US

Funding

Phagosomal Signals Shape Inflammatory Responses to B. BurgdorferiR01AI090166 · NIAID · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI SALAZAR, JUAN C · 2011 to 2015
$2.1M
Phagosomal Signals Shape Inflammatory Responses to Borrelia BurgdorferiR56AI090166 · NIAID · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI SALAZAR, JUAN C · 2010 to 2010
$416k
NIAID NIH HHS AI090166NIAID NIH HHS R01 AI090166NIAID NIH HHS R56 AI090166
6 · The paper itself

Abstract

Phagocytosed Borrelia burgdorferi (Bb), the Lyme disease spirochete, induces a robust and complex innate immune response in human monocytes, in which TLR8 cooperates with TLR2 in the induction of NF-κB-mediated cytokine production, whereas TLR8 is solely responsible for transcription of IFN-β through IRF7. We now establish the role of Bb RNA in TLR8-mediated induction of IFN-β. First, using TLR2-transfected HEK.293 cells, which were unable to phagocytose intact Bb, we observed TLR2 activation by lipoprotein-rich borrelial lysates and TLR2 synthetic ligands but not in response to live spirochetes. Purified Bb RNA, but not borrelial DNA, triggered TLR8 activation. Neither of these 2 ligands induced activation of TLR7. Using purified human monocytes we then show that phagocytosed live Bb, as well as equivalent amounts of borrelial RNA delivered into the phagosome by polyethylenimine (PEI), induces transcription of IFN-β and secretion of TNF-α. The cytokine response to purified Bb RNA was markedly impaired in human monocytes naturally deficient in IRAK-4 and in cells with knockdown TLR8 expression by small interfering RNA. Using confocal microscopy we provide evidence that TLR8 colocalizes with internalized Bb RNA in both early (EEA1) and late endosomes (LAMP1). Live bacterial RNA staining indicates that spirochetal RNA does not transfer from the phagosome into the cytosol. Using fluorescent dextran particles we show that phagosomal integrity in Bb-infected monocytes is not affected. We demonstrate, for the first time, that Bb RNA is a TLR8 ligand in human monocytes and that transcription of IFN-β in response to the spirochete is induced from within the phagosomal vacuole through the TLR8-MyD88 pathway.

Indexed as

Borrelia burgdorferiFemaleGene Knockdown TechniquesHEK293 CellsHumansInterferon-betaInterleukin-1 Receptor-Associated KinasesLyme DiseaseMaleMonocytesMyeloid Differentiation Factor 88PhagosomesRNA, BacterialToll-Like Receptor 7Toll-Like Receptor 8Transcription, GeneticInterferon-betaInterleukin-1 Receptor-Associated KinasesIRAK4 protein, humanMYD88 protein, humanMyeloid Differentiation Factor 88RNA, BacterialTLR7 protein, humanTLR8 protein, humanToll-Like Receptor 7Toll-Like Receptor 8bacterial RNABorrelia burgdorferihuman monocytesTLR8

Identifiers

PMID23906644
PMCPMC3828603
OpenAlexW2015823325

What OpenQuestion holds

Textmetadata
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.