Oral Epithelial Cell Sensing of LPS: A Novel Protection Mechanism of Oral Epithelium

Abstract

The oral epithelium plays a pivotal role in protecting the underlying periodontal tissues from the microbial community found in the periodontal pockets. Having an appropriate phenotype displayed by oral epithelial cells (OECs) is a critical host component required for protection against bacterial invasion into gingival tissues. In the present study, oral epithelial homeostasis associated with the CXCL-8/IL-8 chemokine response was investigated in vitro to determine the mechanisms which OECs utilize for sensing gram-positive and gram-negative microorganisms. The findings of this study have demonstrated a heterogeneous responsiveness of OECs by Toll-like receptor (TLR) 2, a lipoprotein sensor. Notably, however, lipopolysaccharide (LPS), a major virulence factor of gram-negative bacteria, is not recognized by OECs unless the LPS is internalized into OECs. Activation of TLR4 in OECs occurs in the endosome, an intracellular event that requires an unidentified mechanism involving protein transport from the Golgi apparatus to the endosome. Although OECs are not able to detect LPS present in the microenvironment, cell wall derived from an oral commensal-turned pathogen Fusobacterium nucleatum promotes LPS internalization that partially involves FadA adhesion function. Cell wall proteins obtained from other pathogenic microbes that induce CXCL-8 fail to interact with intracellular TLR4 in OECs. Collectively, TLR4 only plays a role when microbial invasion or cell wall uptake occurs in the oral epithelium and thus partially contributes to CXCL-8–mediated periodontal homeostasis. This study has identified a unique LPS sensing mechanism of the oral epithelium to overcome a periodontal infection associated with LPS derived from gram-negative microbes that arises during dysbiosis.