Evidence map›Paper›PMID 25205813›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Invariant natural killer T cells act as an extravascular cytotoxic barrier for joint-invading Lyme Borrelia.

Woo-Yong Lee, Maria-Jesus Sanz, Connie H Y Wong, Pierre-Olivier Hardy, Aydan Salman-Dilgimen, Tara J Moriarty, George Chaconas, Adriana Marques, Roman Krawetz, Christopher H Mody and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

43 citing papers in PubMed, 67 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Cell-Mediated Cytotoxicity in Lyme Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2023
    Article
  10. Article
  11. Role of NK-Like CD8Infection and immunity · 2022
    Article
  12. Article
  13. Review
  14. Article
  15. Live Imaging.Current issues in molecular biology · 2021
    Review
  16. Article
  17. Actually Seeing What Is Going on - Intravital Microscopy in Tissue Engineering.Frontiers in bioengineering and biotechnology · 2021
    Review
  18. Article
  19. Lyme Disease Pathogenesis.Current issues in molecular biology · 2021
    Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 5 institutions in 4 countries.

Woo-Yong LeeCalvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada T2N 4N1; Department of Physiology and Pharmacology.
Maria-Jesus SanzDepartment of Pharmacology, Faculty of Medicine, and Institute of Health Research, INCLIVA, University of Valencia, E46010 Valencia, Spain; and.
Connie H Y WongCalvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada T2N 4N1; Department of Physiology and Pharmacology.
Pierre-Olivier HardyCalvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada T2N 4N1; Department of Microbiology and Infectious Diseases.
Aydan Salman-DilgimenCalvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada T2N 4N1; Department of Biochemistry and Molecular Biology.
Tara J MoriartyCalvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada T2N 4N1; Department of Biochemistry and Molecular Biology.
George ChaconasCalvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada T2N 4N1; Department of Microbiology and Infectious Diseases, Department of Biochemistry and Molecular Biology.
Adriana MarquesClinical Studies Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Roman KrawetzDepartment of Surgery, Department of Cell Biology and Anatomy.
Christopher H ModyCalvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada T2N 4N1; Department of Microbiology and Infectious Diseases, Department of Internal Medicine, and.
Paul KubesCalvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada T2N 4N1; Department of Physiology and Pharmacology, pkubes@ucalgary.ca.
University of Calgary · CAINCLIVA Health Research Institute · ESInstitute of Cell Biology and Neurobiology · ITNational Institute of Allergy and Infectious Diseases · USOffice of Infectious Diseases · US

Funding

Assessment Of Patients With Borrelia InfectionZIAAI000695 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI MARQUES, ADRIANA R · 2009 to 2025
$8.8M
Canadian Institutes of Health Research MOP-53086
6 · The paper itself

Abstract

CXCR6-GFP(+) cells, which encompass 70% invariant natural killer T cells (iNKT cells), have been found primarily patrolling inside blood vessels in the liver. Although the iNKT cells fail to interact with live pathogens, they do respond to bacterial glycolipids presented by CD1d on liver macrophage that have caught the microbe. In contrast, in this study using dual laser multichannel spinning-disk intravital microscopy of joints, the CXCR6-GFP, which also made up 60-70% iNKT cells, were not found in the vasculature but rather closely apposed to and surrounding the outside of blood vessels, and to a lesser extent throughout the extravascular space. These iNKT cells also differed in behavior, responding rapidly and directly to joint-homing pathogens like Borrelia burgdorferi, which causes Lyme disease. These iNKT cells interacted with B. burgdorferi at the vessel wall and disrupted dissemination attempts by these microbes into joints. Successful penetrance of B. burgdorferi out of the vasculature and into the joint tissue was met by a lethal attack by extravascular iNKT cells through a granzyme-dependent pathway, an observation also made in vitro for iNKT cells from joint but not liver or spleen. These results suggest a novel, critical extravascular iNKT cell immune surveillance in joints that functions as a cytotoxic barrier and explains a large increase in pathogen burden of B. burgdorferi in the joint of iNKT cell-deficient mice, and perhaps the greater susceptibility of humans to this pathogen because of fewer iNKT cells in human joints.

Indexed as

Immunity, CellularAnimalsBorrelia burgdorferiGranzymesHumansJoint DiseasesJointsLiverLyme DiseaseMiceMice, Inbred BALB CMice, TransgenicNatural Killer T-CellsOrgan SpecificitySpleenGranzymesgranzyme Bjoint iNKT cellsLyme arthritis

Identifiers

PMID25205813
PMCPMC4183287
OpenAlexW2169092480

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.