TY - JOUR
T1 - Effect of Porphyromonas gingivalis outer membrane vesicles on gingipain-mediated detachment of cultured oral epithelial cells and immune responses
AU - Nakao, Ryoma
AU - Takashiba, Shogo
AU - Kosono, Saori
AU - Yoshida, Minoru
AU - Watanabe, Haruo
AU - Ohnishi, Makoto
AU - Senpuku, Hidenobu
N1 - Funding Information:
We thank Dr. Mike A. Curtis for kindly providing precious materials. This study was supported in part by Grants-in-Aid from JSPS KAKENHI ( 15390571 , 17791348 , 19791360 , 21390506 , 22390397 , and 22791822 ); the Ministry of Health, Labor and Welfare (H22 Iryo-Ippan-026); the Japan Health Science Foundation (No. KHC3308 ); and The Naito Foundation .
PY - 2014/1
Y1 - 2014/1
N2 - 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.
AB - 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.
KW - Cell detachment
KW - Gingipains
KW - Immune responses
KW - Outer membrane vesicles
KW - Porphyromonas gingivalis
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U2 - 10.1016/j.micinf.2013.10.005
DO - 10.1016/j.micinf.2013.10.005
M3 - Article
C2 - 24140554
AN - SCOPUS:84892484811
SN - 1286-4579
VL - 16
SP - 6
EP - 16
JO - Microbes and Infection
JF - Microbes and Infection
IS - 1
ER -
