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

A. Alam, G. Leoni, C. C. Wentworth, J. M. Kwal, H. Wu, C. S. Ardita, P. A. Swanson, J. D. Lambeth, R. M. Jones, A. Nusrat, A. S. Neish

Research output: Contribution to journalArticlepeer-review

120 Scopus citations

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.

Original languageEnglish
Pages (from-to)645-655
Number of pages11
JournalMucosal Immunology
Volume7
Issue number3
DOIs
StatePublished - May 2014

Bibliographical note

Funding Information:
We thank Dr Charles Parkos for critically reviewing the manuscript. This work was supported by grants RO1DK089763, RO1DK055679 (to A.S.N.), 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.

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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