Evidence map›Paper›PMID 29768179›Full record

ArticleImmunity2018

Intestinal Epithelial Wnt Signaling Mediates Acetylcholine-Triggered Host Defense against Infection.

Sid Ahmed Labed, Khursheed A Wani, Sakthimala Jagadeesan, Abdul Hakkim, Mehran Najibi, Javier Elbio Irazoqui

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Immunity, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
–field-weighted citation impact
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

64 citing papers in PubMed.

  1. Cholinergic activation of HLH-30/TFEB promotesbioRxiv : the preprint server for biology · 2026
    Article
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  15. Article
  16. bioRxiv : the preprint server for biology · 2025
    Article
  17. Article
  18. Neuroimmune Circuits in Allergic Diseases.Annual review of immunology · 2025
    Review
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Sid Ahmed LabedCenter for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, MA 02114, USA; Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Khursheed A WaniDepartment of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Sakthimala JagadeesanDepartment of Molecular Biology, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, MA 02114, USA.
Abdul HakkimDepartment of Molecular Biology, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, MA 02114, USA.
Mehran NajibiCenter for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, MA 02114, USA; Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Javier Elbio IrazoquiCenter for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, MA 02114, USA; Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: javier.irazoqui@umassmed.edu.

Funding

Enhancing and expanding the CGC Strain CollectionP40OD010440 · OD · UNIVERSITY OF MINNESOTA · PI Aric L Daul, Ann E. Rougvie · 2012 to 2026
$7.5M
Role of MiT Transcription Factors in Host Defense Against Bacterial InfectionR01GM101056 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI IRAZOQUI, JAVIER ELBIO · 2012 to 2022
$3.9M
NIGMS NIH HHS R01 GM101056NIH HHS P40 OD010440
6 · The paper itself

Abstract

Regulated antimicrobial peptide expression in the intestinal epithelium is key to defense against infection and to microbiota homeostasis. Understanding the mechanisms that regulate such expression is necessary for understanding immune homeostasis and inflammatory disease and for developing safe and effective therapies. We used Caenorhabditis elegans in a preclinical approach to discover mechanisms of antimicrobial gene expression control in the intestinal epithelium. We found an unexpected role for the cholinergic nervous system. Infection-induced acetylcholine release from neurons stimulated muscarinic signaling in the epithelium, driving downstream induction of Wnt expression in the same tissue. Wnt induction activated the epithelial canonical Wnt pathway, resulting in the expression of C-type lectin and lysozyme genes that enhanced host defense. Furthermore, the muscarinic and Wnt pathways are linked by conserved transcription factors. These results reveal a tight connection between the nervous system and the intestinal epithelium, with important implications for host defense, immune homeostasis, and cancer.

Indexed as

AcetylcholineAnimalsAntimicrobial Cationic PeptidesBacteriaCaenorhabditis elegansCaenorhabditis elegans ProteinsGene ExpressionHomeostasisHost-Pathogen InteractionsIntestinal MucosaNeuronsWnt Signaling PathwayAcetylcholineAntimicrobial Cationic PeptidesCaenorhabditis elegans ProteinsCaenorhabditis eleganscholinergichost defenseinfectioninnate immunityintestinal epitheliummuscarinicnervous systemStaphylococcus aureusWnt

Identifiers

PMID29768179
PMCPMC5959051

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Registered trials

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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.