Redox signaling regulates commensal-mediated mucosal homeostasis and restitution and requires formyl peptide receptor 1

• Type of Material: Article
• Authors: Mohammad Alam, Emory University; Giovanna Leoni, Emory University; Christy C. Wentworth, Emory University; Jaclyn M. Kwal, Emory University; Huixia Wu, Emory University; Courtney S. Ardita, Emory University; Phillip Swanson, Emory University; John Lambeth, Emory University; Rheinallt M. Jones, Emory University; Asma Nusrat, Emory University; Andrew Neish, Emory University
• Language: English
• Date: 2014-05-01
• Publisher: Nature Publishing Group
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2014 Society for Mucosal Immunology.
• Final Published Version (URL): http://dx.doi.org/10.1038/mi.2013.84
• Title of Journal or Parent Work: Mucosal Immunology
• ISSN: 1933-0219
• Volume: 7
• Issue: 3
• Start Page: 645
• End Page: 655
• Grant/Funding Information: Supported by grants RO1DK089763, RO1DK055679 to ASN; RO1AI64462 to A.N. and the Emory Digestive Diseases Research Development Center Core Grant (DK 064399).; A.A. is supported by a Research Fellowship from Crohn’s and Colitis Foundation of America.
• Keywords: EPITHELIAL-CELLS; INFLAMMATORY-BOWEL-DISEASE; IN-VIVO; FOCAL ADHESION KINASE; Life Sciences & Biomedicine; Science & Technology; Immunology; ACTIVATION; PHOSPHATASE; PATHWAY; MIGRATION; CELL-PROLIFERATION; NEUTROPHILS
• Research Categories: Health Sciences, Immunology; Health Sciences, Pathology

Abstract

The mammalian gut microbiota is essential for normal intestinal development, renewal, and repair. Injury to the intestinal mucosa can occur with infection, surgical trauma, and in idiopathic inflammatory bowel disease. Repair of mucosal injury, termed restitution, as well as restoration of intestinal homeostasis involves induced and coordinated proliferation and migration of intestinal epithelial cells. N-formyl peptide receptors (FPRs) are widely expressed pattern recognition receptors that can specifically bind and induce responses to host-derived and bacterial peptides and small molecules. Here we report that specific members of the gut microbiota stimulate FPR1 on intestinal epithelial cells to generate reactive oxygen species via enterocyte NADPH oxidase 1 (NOX1), causing rapid phosphorylation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase mitogen-activated protein kinase. These events stimulate migration and proliferation of enterocytes adjacent to colonic wounds. Taken together, these findings identify a novel role of FPR1 as pattern recognition receptors for perceiving the enteric microbiota that promotes repair of mucosal wounds via generation of reactive oxygen species from the enterocyte NOX1.