Intestinal Epithelial Wnt Signaling Mediates Acetylcholine-Triggered Host Defense against Infection
Department of Microbiology and Physiological Systems
Immunology and Infectious Disease | Microbiology
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.
Caenorhabditis elegans, Staphylococcus aureus, Wnt, cholinergic, host defense, infection, innate immunity, intestinal epithelium, muscarinic, nervous system
DOI of Published Version
Immunity. 2018 May 15;48(5):963-978.e3. doi: 10.1016/j.immuni.2018.04.017. Link to article on publisher's site
Labed SA, Wani KA, Jagadeesan S, Hakkim A, Najibi M, Irazoqui JE. (2018). Intestinal Epithelial Wnt Signaling Mediates Acetylcholine-Triggered Host Defense against Infection. Microbiology and Physiological Systems Publications. https://doi.org/10.1016/j.immuni.2018.04.017. Retrieved from https://escholarship.umassmed.edu/maps_pubs/72