Intestinal Epithelial Wnt Signaling Mediates Acetylcholine-Triggered Host Defense Against Infection

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2018 May 17

PMID 29768179

Citations 45

Authors

Sid Ahmed Labed

Khursheed A Wani

Sakthimala Jagadeesan

Abdul Hakkim

Mehran Najibi

Javier Elbio Irazoqui

Affiliations

Soon will be listed here.

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.

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