Evidence map›Paper›PMID 27064448›Full record

ArticleNature medicine2016

Nod2-mediated recognition of the microbiota is critical for mucosal adjuvant activity of cholera toxin.

Donghyun Kim, Yun-Gi Kim, Sang-Uk Seo, Dong-Jae Kim, Nobuhiko Kamada, Dave Prescott, Mathias Chamaillard, Dana J Philpott, Philip Rosenstiel, Naohiro Inohara and 1 more

Erratum issuedAbstract read
In one paragraph

Article in Nature medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 80 papers.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed
7.8field-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

80 citing papers in PubMed, 117 citations in OpenAlex.

  1. Pediatrics · 2019
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  18. Metabolic fitness of IgAMucosal immunology · 2024
    Article
  19. Article
  20. Article

20 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 3 countries.

Donghyun KimDepartment of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA.ORCID 0000-0002-5137-2213
Yun-Gi KimDepartment of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Sang-Uk SeoDepartment of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Dong-Jae KimDepartment of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Nobuhiko KamadaDepartment of Internal Medicine, Division of Gastroenterology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Dave PrescottDepartment of Immunology, University of Toronto, Toronto, Ontario, Canada.
Mathias Chamaillard
Dana J PhilpottDepartment of Immunology, University of Toronto, Toronto, Ontario, Canada.
Philip RosenstielInstitute of Clinical Molecular Biology, University of Kiel, Kiel, Germany.
Naohiro InoharaDepartment of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Gabriel NúñezDepartment of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
University of Michigan · USUniversity of Toronto · CACenter for Infection and Immunity of Lille · FR

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI THEODORE S LAWRENCE · 1988 to 2026
$178.2M
University of Michigan Center for Gastrointestinal ResearchP30DK034933 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI OWYANG, CHUNG · 1986 to 2021
$22.5M
Nod2: A Susceptibility Gene for Crohn's DiseaseR01DK061707 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI NUNEZ, GABRIEL · 2002 to 2017
$4.7M
NCI NIH HHS P30 CA046592NIDDK NIH HHS P30 DK034933NIDDK NIH HHS R01 DK061707
6 · The paper itself

Abstract

Cholera toxin (CT) is a potent adjuvant for inducing mucosal immune responses. However, the mechanism by which CT induces adjuvant activity remains unclear. Here we show that the microbiota is critical for inducing antigen-specific IgG production after intranasal immunization. After mucosal vaccination with CT, both antibiotic-treated and germ-free (GF) mice had reduced amounts of antigen-specific IgG, smaller recall-stimulated cytokine responses, impaired follicular helper T (TFH) cell responses and reduced numbers of plasma cells. Recognition of symbiotic bacteria via the nucleotide-binding oligomerization domain containing 2 (Nod2) sensor in cells that express the integrin CD11c (encoded by Itgax) was required for the adjuvanticity of CT. Reconstitution of GF mice with a Nod2 agonist or monocolonization with Staphylococcus sciuri, which has high Nod2-stimulatory activity, was sufficient to promote robust CT adjuvant activity, whereas bacteria with low Nod2-stimulatory activity did not. Mechanistically, CT enhanced Nod2-mediated cytokine production in dendritic cells via intracellular cyclic AMP. These results show a role for the microbiota and the intracellular receptor Nod2 in promoting the mucosal adjuvant activity of CT.

Indexed as

Acetylmuramyl-Alanyl-IsoglutamineAdjuvants, ImmunologicAnimalsAnti-Bacterial AgentsCD11c AntigenCholera ToxinCyclic AMPCytokinesDendritic CellsEnzyme-Linked Immunospot AssayFlow CytometryGerm-Free LifeImmunity, MucosalMiceMice, KnockoutMicrobiotaAcetylmuramyl-Alanyl-IsoglutamineAdjuvants, ImmunologicAnti-Bacterial AgentsCD11c AntigenCholera ToxinCyclic AMPCytokinesNod2 protein, mouseNod2 Signaling Adaptor Protein

Identifiers

PMID27064448
PMCPMC4860092
OpenAlexW2320311613

What OpenQuestion holds

Textmetadata
LicenceTDM
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.