Abstract
Epithelial cells (ECs) continuously interact with microorganisms and detect their presence via different pattern-recognition receptors (PRRs) including Toll-like receptors (TLRs). Ligation of epithelial TLRs by pathogens is usually associated with the induction of pro-inflammatory mediators and antimicrobial factors. In this study, using human airway ECs as a model, we found that detection of microbial patterns via epithelial TLRs directly regulates tissue homeostasis. Staphylococcus aureus (S. aureus) and microbial patterns signaling via TLR2 and TLR5 induce a set of non-immune epithelial responses including cell migration, wound repair, proliferation, and survival of primary and cancerous ECs. Using small interfering RNA (siRNA) gene targeting, receptor-tyrosine kinase microarray and inhibition studies, we determined that TLR and the epidermal growth factor receptor (EGFR) mediate the stimulating effect of microbial patterns on epithelial repair. Microbial patterns signaling via Toll-like receptors 2 and 5 contribute to epithelial repair, growth and survival. This effect is independent of hematopoietic and other cells as well as inflammatory cytokines suggesting that epithelia are able to regulate their integrity in an autonomous non-inflammatory manner by sensing microbes directly via TLRs.
Highlights
Epithelial cells (ECs) cover the body surfaces and represent a primary site of host-microbe interactions [1]
We have found that S. aureus as well as various microbial products signaling via TLR2 and TLR5 directly induce epithelial repair, survival and growth, and that such compensatory epithelial responses are mediated by an autonomous non-inflammatory pathway linking Toll-like receptors (TLRs) and epidermal growth factor receptor (EGFR) in ECs
To test whether bacteria are able to induce epithelial repair, we selected an experimental in vitro model, in which wounded airway epithelium is stimulated with inactivated whole S. aureus, one of the Academic Editor: Derya Unutmaz, New York University School of Medicine, United States of America
Summary
Epithelial cells (ECs) cover the body surfaces and represent a primary site of host-microbe interactions [1]. It has been shown that MyD88-mediated signaling induced by commensal flora in intestinal mucosal cells is important for the regulation of epithelial homeostasis under steady-state conditions and for the expression of protective molecules in ECs following mucosal injury [5]. Activation of NF-kB, a transcription factor involved in the response to many danger factors including TLR ligands [10], is currently associated with an altered epithelial homeostasis and cancer development [11]. Until now, it remaines obscure whether microbes are able to induce epithelial repair directly, i.e. independently of inflammatory cells and mediators
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