Formylated Peptide Receptor Mediated Commensal‐Epithelial Signaling

Abstract

Commensal bacteria and/or their products engender beneficial effects on the mammalian gut, including promotion of homeostatic cellular turnover and enhanced wound healing. These bacteria have also been shown to activate the pro‐growth ERK signaling pathway, while having no stimulatory effects on the pro‐inflammatory NFkappaB or JNK pathways. Here we examine a mechanism by which luminal commensal bacteria activate gut epithelial ERK signaling. Polarized model epithelial cells (T84) were apically incubated with a panel of commensal bacteria for up to 30 min. All commensal bacteria tested potently induced ERK phosphorylation, but not IkappaB or JNK phosphorylation. This specific phosphorylation of ERK was recapitulated using apical purified bacterial peptide N‐formyl‐Met‐Leu‐Phe (fMLF). Host cells perceive fMLF via formylated peptide receptors (FPR) located on the apical surface of gut epithelial cells. Apical commensal or fMLF treatment resulted in the activation of FPR. Also, pretreatment of model epithelia with BOC2 (a specific peptide antagonist) or pertussis toxin (a Gi‐protein inhibitor) abolished commensal mediated ERK phosphorylation. Together, these data show that commensal bacteria specifically activate the pro‐growth ERK pathway in an FPR dependent manner, and suggests a mechanism by which commensal bacteria contributes to gut epithelial cellular turnover.