Porphyromonas gingivalis induces penetration of lipopolysaccharide and peptidoglycan through the gingival epithelium via degradation of junctional adhesion molecule 1

Autoři: Hiroki Takeuchi aff001;  Naoko Sasaki aff002;  Shunsuke Yamaga aff001;  Masae Kuboniwa aff001;  Michiya Matsusaki aff002;  Atsuo Amano aff001
Působiště autorů: Department of Preventive Dentistry, Graduate School of Dentistry, Osaka University, Suita-Osaka, Japan aff001;  Joint Research Laboratory (TOPPAN) for Advanced Cell Regulatory Chemistry, Graduate School of Engineering, Osaka University, Suita-Osaka, Japan aff002;  Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Suita-Osaka, Japan aff003
Vyšlo v časopise: Porphyromonas gingivalis induces penetration of lipopolysaccharide and peptidoglycan through the gingival epithelium via degradation of junctional adhesion molecule 1. PLoS Pathog 15(11): e32767. doi:10.1371/journal.ppat.1008124
Kategorie: Research Article
doi: 10.1371/journal.ppat.1008124


Porphyromonas gingivalis is a major pathogen in severe and chronic manifestations of periodontal disease, which is one of the most common infections of humans. A central feature of P. gingivalis pathogenicity is dysregulation of innate immunity at the gingival epithelial interface; however, the molecular basis underlying P. gingivalis–dependent abrogation of epithelial barrier function remains unknown. Gingival epithelial cells express junctional adhesion molecule (JAM1), a tight junction–associated protein, and JAM1 homodimers regulate epithelial barrier function. Here we show that Arg-specific or Lys-specific cysteine proteases (gingipains) secreted by P. gingivalis can specifically degrade JAM1 at K134 and R234 in gingival epithelial cells, resulting in permeability of the gingival epithelium to 40 kDa dextran, lipopolysaccharide (LPS), and proteoglycan (PGN). A P. gingivalis strain lacking gingipains was impaired in degradation of JAM1. Knockdown of JAM1 in monolayer cells and a three-dimensional multilayered tissue model also increased permeability to LPS, PGN, and gingipains. Inversely, overexpression of JAM1 in epithelial cells prevented penetration by these agents following P. gingivalis infection. Our findings strongly suggest that P. gingivalis gingipains disrupt barrier function of stratified squamous epithelium via degradation of JAM1, allowing bacterial virulence factors to penetrate into subepithelial tissues.

Klíčová slova:

Cell staining – Confocal microscopy – Epithelial cells – Epithelium – Immunoblotting – Permeability – Staining – Bacterial cultures


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