Evidence map›Paper›PMID 23776172›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2013

β-Defensin 2 and 3 promote the uptake of self or CpG DNA, enhance IFN-α production by human plasmacytoid dendritic cells, and promote inflammation.

Poonam Tewary, Gonzalo de la Rosa, Neeraj Sharma, Luis G Rodriguez, Sergey G Tarasov, O M Zack Howard, Hidekazu Shirota, Folkert Steinhagen, Dennis M Klinman, De Yang and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
8.0field-weighted citation impact, top 2% 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

57 citing papers in PubMed, 110 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. DNA-Dependent Interferon Induction and Lung Inflammation inJournal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2023
    Article
  9. Review
  10. Mechanisms and regulation of defensins in host defense.Signal transduction and targeted therapy · 2023
    Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Immunomodulatory and Allergenic Properties of Antimicrobial Peptides.International journal of molecular sciences · 2022
    Review
  16. Review
  17. Review
  18. The Pharmacodynamics Study of Insect Defensin DLP4 Against ToxigenicFrontiers in cellular and infection microbiology · 2021
    Article
  19. Human β-defensin-3 participates in intra-amniotic host defense in women with labor at term, spontaneous preterm labor and intact membranes, and preterm prelabor rupture of membranes.The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians · 2020
    Article
  20. Article
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

11 authors at 4 institutions in 1 country.

Poonam TewaryLaboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Laboratory for Cancer Research, Frederick, MD 21702, USA. tewaryp@mail.nih.gov
Gonzalo de la Rosa
Neeraj Sharma
Luis G Rodriguez
Sergey G Tarasov
O M Zack Howard
Hidekazu Shirota
Folkert Steinhagen
Dennis M Klinman
De Yang
Joost J Oppenheim
National Cancer Institute · USCenter for Cancer Research · USFrederick National Laboratory for Cancer Research · USScience Applications International Corporation (United States) · US

Funding

Studies of Receptor Interactions and Effects of AlarminsZIABC009369 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI OPPENHEIM, JOOST J · 2009 to 2022
$16.5M
Mechanism of action and therapeutic utility of stimulatory CpG oligonucleotidesZIABC010852 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI KLINMAN, DENNIS · 2009 to 2019
$11.3M
CCR Biophysics Resource CoreZICBC010965 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI TARASOV, SERGEY · 2009 to 2025
$10.5M
CCR NIH HHS HHSN261200800001CIntramural NIH HHS ZIA BC009369NCI NIH HHS HHSN261200800001E
6 · The paper itself

Abstract

Alarmins are a group of structurally diverse host defense antimicrobial peptides that are important immune activators. In this article, we present a novel role for two potent alarmins, human β-defensin 2 and 3 (HBD2 and 3), in promoting IFN-α production by human plasmacytoid dendritic cells. We demonstrate that HBD2 and 3 activate pDCs by enhancing the intracellular uptake of CpG and self DNA and promote DNA-induced IFN-α production in a TLR9-dependent manner. Both CpG and host DNA form aggregates that resemble DNA nets when combined with HBD2 and 3. Isothermal titration calorimetry studies to elucidate the nature of HBD3/CpG complexes demonstrate involvement of enthalpy-driven interactions, in addition to hydrophobic interactions, with the formation of complexes at a molar ratio of 2:1 defensin/CpG. The i.v. administration of HBD3/CpG complexes induced proinflammatory cytokines like IL-12, IFN-γ, IL-6, IFN-α, and IL-10 in serum, associated with an increased recruitment of APCs in the spleen. Subcutaneous injections of these complexes showed enhanced infiltration of inflammatory cells at the injection site, indicating a potential pathophysiological role for alarmin/DNA complexes in contributing to inflammation. Intraperitoneal immunization of HBD3/CpG complexes with OVA enhanced both cellular and humoral responses to OVA, compared with OVA/HBD3 or OVA/CPG alone, indicative of a much more potent adjuvant effect of the HBD3/CpG complexes. Thus, the ability of defensins to enhance cellular uptake of nucleic acids can lead to improved vaccine formulations by promoting their uptake by various cells, resulting in an enhanced immune response.

Indexed as

Adjuvants, ImmunologicAnimalsAntigen-Presenting Cellsbeta-DefensinsBiological TransportCells, CulturedCpG IslandsDendritic CellsDNAFemaleHumansHydrophobic and Hydrophilic InteractionsInflammationInterferon-alphaInterferon-gammaInterleukin-12Adjuvants, Immunologicbeta-DefensinsDEFB103A protein, humanDEFB4A protein, humanDNAInterferon-alphaInterferon-gammaInterleukin-12Interleukin-6OvalbuminTLR9 protein, humanToll-Like Receptor 9

Identifiers

PMID23776172
PMCPMC4433160
OpenAlexW2165731518

What OpenQuestion holds

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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.