Cholinergic Receptor-Wnt Pathway Controls Immune Activation by Sensing Intestinal Dysfunction

Authors

Jie Ren
Yu Sang
Alejandro Aballay

Publication Date

11-1-2022

Journal

Cell Reports

Abstract

Alterations in the intestinal physiology caused by pathogen colonization result in immune activation. To provide insights into the mechanisms underlying the control of immune activation by changes in intestinal homeostasis, we conducted a forward genetic screen for suppressors of immune activation by intestinal distension in Caenorhabditis elegans. Our results indicate that C. elegans ACC-4, a member of a family of acetylcholine receptors, is required in immune activation by defects in the defecation motor program or by pathogen infection. ACC-4 acts postsynaptically in non-cholinergic RIM neurons to regulate several immune genes and a Wnt-mediated host immune response. These findings uncover a gut-brain-microbial axis that uses neural cholinergic signaling and the Wnt pathway to control immune activation in response to alterations in intestinal homeostasis.

Keywords

Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Receptors, Cholinergic, Wnt Signaling Pathway, Cholinergic Agents

Comments

Supplementary Material

PMID: 36323254

DOI

10.1016/j.celrep.2022.111575

PMID

36323254

PMCID

PMC9699718

PubMedCentral® Posted Date

November 2022

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes