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

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    Authors
    Labed, Sid Ahmed
    Wani, Khursheed A.
    Jagadeesan, Sakthimala
    Hakkim, Abdul
    Najibi, Mehran
    Irazoqui, Javier E.
    UMass Chan Affiliations
    Department of Microbiology and Physiological Systems
    Document Type
    Journal Article
    Publication Date
    2018-05-15
    Keywords
    Caenorhabditis elegans
    Staphylococcus aureus
    Wnt
    cholinergic
    host defense
    infection
    innate immunity
    intestinal epithelium
    muscarinic
    nervous system
    Immunology and Infectious Disease
    Microbiology
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    Link to Full Text
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5959051/
    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.
    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.2018.04.017
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/36512
    PubMed ID
    29768179
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    Link to Article in PubMed

    ae974a485f413a2113503eed53cd6c53
    10.1016/j.immuni.2018.04.017
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