Intestinal Epithelial Wnt Signaling Mediates Acetylcholine-Triggered Host Defense against Infection
Name:
Publisher version
View Source
Access full-text PDFOpen Access
View Source
Check access options
Check access options
Authors
Labed, Sid AhmedWani, Khursheed A.
Jagadeesan, Sakthimala
Hakkim, Abdul
Najibi, Mehran
Irazoqui, Javier E.
UMass Chan Affiliations
Department of Microbiology and Physiological SystemsDocument Type
Journal ArticlePublication Date
2018-05-15Keywords
Caenorhabditis elegansStaphylococcus aureus
Wnt
cholinergic
host defense
infection
innate immunity
intestinal epithelium
muscarinic
nervous system
Immunology and Infectious Disease
Microbiology
Metadata
Show full item recordAbstract
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.Source
Immunity. 2018 May 15;48(5):963-978.e3. doi: 10.1016/j.immuni.2018.04.017. Link to article on publisher's site
DOI
10.1016/j.immuni.2018.04.017Permanent Link to this Item
http://hdl.handle.net/20.500.14038/36512PubMed ID
29768179Related Resources
ae974a485f413a2113503eed53cd6c53
10.1016/j.immuni.2018.04.017