Evidence map›Paper›PMID 23447566›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2013

Host DNA released in response to aluminum adjuvant enhances MHC class II-mediated antigen presentation and prolongs CD4 T-cell interactions with dendritic cells.

Amy S McKee, Matthew A Burchill, Michael W Munks, Lei Jin, John W Kappler, Rachel S Friedman, Jordan Jacobelli, Philippa Marrack

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed, 1 pooled it
7.2field-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

81 citing papers in PubMed, 1 synthesis or guideline pooled it, 137 citations in OpenAlex.

  1. Pooled it
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  15. Emerging adjuvants for intradermal vaccination.International journal of pharmaceutics · 2023
    Review
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21 more citing papers are in PubMed but not listed here.

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

8 authors at 5 institutions in 1 country.

Amy S McKeeClinical Immunology Division, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Matthew A Burchill
Michael W Munks
Lei Jin
John W Kappler
Rachel S Friedman
Jordan Jacobelli
Philippa Marrack
University of Colorado Denver · USHoward Hughes Medical Institute · USNational Jewish Health · USUniversity of Colorado Anschutz Medical Campus · USUniversity of Colorado Health · US

Funding

THE REGULATION OF V ALPHA 7 EXPRESSING T CELLSP01AI022295 · NIAID · NATIONAL JEWISH HEALTH · PI REFAELI, YOSEF · 1985 to 2011
$11.7M
CHARACTERISTICS OF T CELL RECEPTORSR01AI018785 · NIAID · NATIONAL JEWISH HEALTH · PI MARRACK, PHILIPPA C. · 1985 to 2022
$7.3M
CHARACTERISTICS OF T-CELL RECEPTORSR37AI018785 · NIAID · NATIONAL JEWISH HEALTH · PI MARRACK, PHILIPPA C. · 1992 to 2001
$522k
Characteristics of T Cell ReceptorsR56AI018785 · NIAID · NATIONAL JEWISH HEALTH · PI MARRACK, PHILIPPA C. · 2012 to 2012
$410k
NIAID NIH HHS AI-18785NIAID NIH HHS AI-22295NIAID NIH HHS P01 AI022295NIAID NIH HHS R01 AI018785NIAID NIH HHS R37 AI018785NIAID NIH HHS R56 AI018785
6 · The paper itself

Abstract

Many vaccines include aluminum salts (alum) as adjuvants despite little knowledge of alum's functions. Host DNA rapidly coats injected alum. Here, we further investigated the mechanism of alum and DNA's adjuvant function. Our data show that DNase coinjection reduces CD4 T-cell priming by i.m. injected antigen + alum. This effect is partially replicated in mice lacking stimulator of IFN genes, a mediator of cellular responses to cytoplasmic DNA. Others have shown that DNase treatment impairs dendritic cell (DC) migration from the peritoneal cavity to the draining lymph node in mice immunized i.p. with alum. However, our data show that DNase does not affect accumulation of, or expression of costimulatory proteins on, antigen-loaded DCs in lymph nodes draining injected muscles, the site by which most human vaccines are administered. DNase does inhibit prolonged T-cell-DC conjugate formation and antigen presentation between antigen-positive DCs and antigen-specific CD4 T cells following i.m. injection. Thus, from the muscle, an immunization site that does not require host DNA to promote migration of inflammatory DCs, alum acts as an adjuvant by introducing host DNA into the cytoplasm of antigen-bearing DCs, where it engages receptors that promote MHC class II presentation and better DC-T-cell interactions.

Indexed as

Adjuvants, ImmunologicAlum CompoundsAnimalsAntigen PresentationAntigensCD4-Positive T-LymphocytesCell CommunicationCell MovementDendritic CellsDNAHistocompatibility Antigens Class IIHumansMiceMice, KnockoutMice, NudeAdjuvants, ImmunologicAlum Compoundsaluminum sulfateAntigensDNAHistocompatibility Antigens Class II

Identifiers

PMID23447566
PMCPMC3607057
OpenAlexW2011050800

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.