title: Effect of Porphyromonas gingivalis outer membrane vesicles on gingipain-mediated detachment of cultured oral epithelial cells and immune responses.
abstract: Porphyromonas gingivalis is a major etiological agent of periodontal diseases and the outer membrane vesicles (OMVs) contain virulence factors such as LPS and gingipains. In this study, we investigated the potential role of the OMVs in host immune response and tissue destruction during P. gingivalis infection. Firstly, we found that sera from periodontitis patients had significantly stronger reactivity against an OMV-producing wild type strain than the isogenic OMV-depleted strain. OMVs were found to be highly antigenic, as absorption of patient sera with OMVs greatly reduced reactivity with whole cells of P. gingivalis. LC-MS/MS analysis of OMVs revealed multiple forms of gingipains and several gingipain-related proteins. Western blots of OMVs using patient sera revealed a conserved immunoreactive antigen profile resembling the profile of OMV antigens that were recognized by gingipain antiserum, suggesting a potential role of OMV-associated gingipains in triggering antibody-mediated immune responses to P. gingivalis infection. When OMVs were added to a monolayer of an oral squamous epithelial cell line, OMVs caused cell detachment, which was inhibited by preincubating OMVs with anti-gingipain antiserum. These data suggest that gingipain-laden OMVs may contribute to tissue destruction in periodontal diseases by serving as a vehicle for the antigens and active proteases.
authors.affiliation: Department of Bacteriology I, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku, Tokyo 162-8640, Japan. Electronic address: ryoma73@nih.go.jp.
authors.forename: Ryoma
authors.initials: R
authors.lastname: Nakao
authors.affiliation: Department of Pathophysiology-Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata, Kita, Okayama, Okayama 700-8525, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Takashiba
authors.affiliation: Biotechnology Research Center, The University of Tokyo, 1-1-1 Yayoi, Bunkyo, Tokyo 113-8657, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Kosono
authors.affiliation: Chemical Genetic Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku, Tokyo 162-8640, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Department of Bacteriology I, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku, Tokyo 162-8640, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ohnishi
authors.affiliation: Department of Bacteriology I, National Institute of Infectious Diseases, 1-23-1, Toyama, Shinjuku, Tokyo 162-8640, Japan.
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Senpuku
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism*; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D016866:Bacteroidaceae Infections / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism* / Q000382:microbiology*; D000080867:Gingipain Cysteine Endopeptidases; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D009061:Mouth Mucosa / Q000382:microbiology*; D016966:Porphyromonas gingivalis / Q000276:immunology* / Q000472:pathogenicity*; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D000080867:Gingipain Cysteine Endopeptidases; D016056:Immunodominant Epitopes; D037521:Virulence Factors; D003546:Cysteine Endopeptidases
keywords: Cell detachment; Gingipains; Immune responses; Outer membrane vesicles; Porphyromonas gingivalis