Evidence map›Paper›PMID 18708593›Full record

ArticleJournal of leukocyte biology2008

TLR4-mediated activation of dendritic cells by the heat shock protein DnaK from Francisella tularensis.

Amit R Ashtekar, Ping Zhang, Jannet Katz, Champion C S Deivanayagam, Prasad Rallabhandi, Stefanie N Vogel, Suzanne M Michalek

Open access · greenAbstract read
In one paragraph

Article in Journal of leukocyte biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

32 citing papers in PubMed, 50 citations in OpenAlex.

  1. Review
  2. The immune response toFrontiers in microbiology · 2025
    Review
  3. International journal of molecular sciences · 2023
    Article
  4. Article
  5. Article
  6. International journal of molecular sciences · 2021
    Article
  7. International journal of molecular sciences · 2021
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Efficacy of Resistance toFrontiers in immunology · 2017
    Article
  15. Innate Immune Recognition: Implications for the Interaction ofFrontiers in cellular and infection microbiology · 2017
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. IL-23 in infections, inflammation, autoimmunity and cancer: possible role in HIV-1 and AIDS.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2012
    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 2 institutions in 1 country.

Amit R AshtekarDepartment of Microbiology, University of Alabama at Birmingham, 845 19th Street South, BBRB 258/5, Birmingham, AL 35294-2170, USA.
Ping Zhang
Jannet Katz
Champion C S Deivanayagam
Prasad Rallabhandi
Stefanie N Vogel
Suzanne M Michalek
University of Alabama at Birmingham · USUniversity of Maryland, Baltimore · US

Funding

Vaccine strategy for broad spectrum protection agains non-typhoidal salmonellU54AI057168 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI LEVINE, MYRON MAX · 2003 to 2013
$91.5M
DIFFERENTIATIVE SIGNALS FOR MACROPHAGE ACTIVATIONR37AI018797 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI VOGEL, STEFANIE N. · 2000 to 2009
$5.3M
DIFFERENTIATIVE SIGNALS FOR MACROPHANGE ACTIVATIONR01AI018797 · NIAID · U.S. UNIFORMED SERVICES UNIV OF HLTH SCI · PI VOGEL, STEFANIE N. · 1985 to 2014
$3.8M
Development of a Mucosal Vaccine Against F. tularensisU01AI056460 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI MICHALEK, SUZANNE M. · 2003 to 2007
$2.5M
Differentiative Signals for Macrophage ActivationR56AI018797 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI VOGEL, STEFANIE N. · 2015 to 2015
$506k
NIAID NIH HHS AI-18797NIAID NIH HHS AI-56460NIAID NIH HHS R01 AI018797NIAID NIH HHS R37 AI018797NIAID NIH HHS R56 AI018797NIAID NIH HHS U01 AI056460NIAID NIH HHS U54 AI057168NIAID NIH HHS U54 AI-57168
6 · The paper itself

Abstract

Francisella tularensis is the causative agent of tularemia, a severe, debilitating disease of humans and other mammals. As this microorganism is also classified as a "category-A pathogen" and a potential biowarfare agent, there is a need for an effective vaccine. Several antigens of F. tularensis, including the heat shock protein DnaK, have been proposed for use in a potential subunit vaccine. In this study, we characterized the innate immune response of murine bone marrow-derived dendritic cells (DC) to F. tularensis DnaK. Recombinant DnaK was produced using a bacterial expression system and purified using affinity, ion-exchange, and size-exclusion chromatography. DnaK induced the activation of MAPKs and NF-kappaB in DC and the production of the proinflammatory cytokines IL-6, TNF-alpha, and IL-12 p40, as well as low levels of IL-10. DnaK induced phenotypic maturation of DC, as demonstrated by an up-regulation of costimulatory molecules CD40, CD80, and CD86. DnaK stimulated DC through TLR4 and the adapters MyD88 and Toll/IL-1R domain-containing adaptor-inducing IFN-beta (TRIF) that mediated differential responses. DnaK induced activation of MAPKs and NF-kappaB in a MyD88- or TRIF-dependent manner. However, the presence of MyD88- and TRIF-dependent signaling pathways was essential for an optimal, DnaK-induced cytokine response in DC. In contrast, DnaK induced DC maturation in a TRIF-dependent, MyD88-independent manner. These results provide insight about the molecular interactions between an immunodominant antigen of F. tularensis and host immune cells, which is crucial for the rational design and development of a safe and efficacious vaccine against tularemia.

Indexed as

Adaptor Proteins, Vesicular TransportAnimalsB7-1 AntigenB7-2 AntigenBlotting, WesternCells, CulturedDendritic CellsEndotoxinsEnzyme-Linked Immunosorbent AssayFlow CytometryFrancisella tularensisHeat-Shock ProteinsHumansInterferon-gammaInterleukin-12KidneyAdaptor Proteins, Vesicular TransportB7-1 AntigenB7-2 AntigenEndotoxinsHeat-Shock ProteinsInterferon-gammaInterleukin-12LipopolysaccharidesMitogen-Activated Protein Kinase KinasesMyd88 protein, mouseMyeloid Differentiation Factor 88NF-kappa BTicam1 protein, mouseTlr2 protein, mouseTlr4 protein, mouseToll-Like Receptor 2Toll-Like Receptor 4Tumor Necrosis Factor-alpha

Identifiers

PMID18708593
PMCPMC2614597
OpenAlexW2142347832

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.