Neisseria gonorrhoeae infects the heterogeneous epithelia of the human cervix using distinct mechanisms.

Sexually transmitted infections are a critical public health issue. However, the mechanisms underlying sexually transmitted infections in women and the link between the infection mechanism and the wide range of clinical outcomes remain elusive due to a lack of research models mimicking human infecti...

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Main Authors: Qian Yu, Liang-Chun Wang, Sofia Di Benigno, Scott D Gray-Owen, Daniel C Stein, Wenxia Song
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2019-12-01
Series:PLoS Pathogens
Online Access:https://doi.org/10.1371/journal.ppat.1008136
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author Qian Yu
Liang-Chun Wang
Sofia Di Benigno
Scott D Gray-Owen
Daniel C Stein
Wenxia Song
author_facet Qian Yu
Liang-Chun Wang
Sofia Di Benigno
Scott D Gray-Owen
Daniel C Stein
Wenxia Song
author_sort Qian Yu
collection DOAJ
description Sexually transmitted infections are a critical public health issue. However, the mechanisms underlying sexually transmitted infections in women and the link between the infection mechanism and the wide range of clinical outcomes remain elusive due to a lack of research models mimicking human infection in vivo. We established a human cervical tissue explant model to mimic local Neisseria gonorrhoeae (GC) infections. We found that GC preferentially colonize the ectocervix by activating integrin-β1, which inhibits epithelial shedding. GC selectively penetrate into the squamocolumnar junction (TZ) and endocervical epithelia by inducing β-catenin phosphorylation, which leads to E-cadherin junction disassembly. Epithelial cells in various cervical regions differentially express carcinoembryonic antigen-related cell adhesion molecules (CEACAMs), the host receptor for GC opacity-associated proteins (OpaCEA). Relatively high levels were detected on the luminal membrane of ecto/endocervical epithelial cells but very low levels intracellularly in TZ epithelial cells. CEACAM-OpaCEA interaction increased ecto/endocervical colonization and reduced endocervical penetration by increasing integrin-β1 activation and inhibiting β-catenin phosphorylation respectively, through CEACAM downstream signaling. Thus, the intrinsic properties of cervical epithelial cells and phase-variation of bacterial surface molecules both play a role in controlling GC infection mechanisms and infectivity, preferential colonization or penetration, potentially leading to asymptomatic or symptomatic infection.
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spelling doaj.art-ac5a3cb5209b46e88ea33a417fe9a2ff2022-12-21T18:30:38ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742019-12-011512e100813610.1371/journal.ppat.1008136Neisseria gonorrhoeae infects the heterogeneous epithelia of the human cervix using distinct mechanisms.Qian YuLiang-Chun WangSofia Di BenignoScott D Gray-OwenDaniel C SteinWenxia SongSexually transmitted infections are a critical public health issue. However, the mechanisms underlying sexually transmitted infections in women and the link between the infection mechanism and the wide range of clinical outcomes remain elusive due to a lack of research models mimicking human infection in vivo. We established a human cervical tissue explant model to mimic local Neisseria gonorrhoeae (GC) infections. We found that GC preferentially colonize the ectocervix by activating integrin-β1, which inhibits epithelial shedding. GC selectively penetrate into the squamocolumnar junction (TZ) and endocervical epithelia by inducing β-catenin phosphorylation, which leads to E-cadherin junction disassembly. Epithelial cells in various cervical regions differentially express carcinoembryonic antigen-related cell adhesion molecules (CEACAMs), the host receptor for GC opacity-associated proteins (OpaCEA). Relatively high levels were detected on the luminal membrane of ecto/endocervical epithelial cells but very low levels intracellularly in TZ epithelial cells. CEACAM-OpaCEA interaction increased ecto/endocervical colonization and reduced endocervical penetration by increasing integrin-β1 activation and inhibiting β-catenin phosphorylation respectively, through CEACAM downstream signaling. Thus, the intrinsic properties of cervical epithelial cells and phase-variation of bacterial surface molecules both play a role in controlling GC infection mechanisms and infectivity, preferential colonization or penetration, potentially leading to asymptomatic or symptomatic infection.https://doi.org/10.1371/journal.ppat.1008136
spellingShingle Qian Yu
Liang-Chun Wang
Sofia Di Benigno
Scott D Gray-Owen
Daniel C Stein
Wenxia Song
Neisseria gonorrhoeae infects the heterogeneous epithelia of the human cervix using distinct mechanisms.
PLoS Pathogens
title Neisseria gonorrhoeae infects the heterogeneous epithelia of the human cervix using distinct mechanisms.
title_full Neisseria gonorrhoeae infects the heterogeneous epithelia of the human cervix using distinct mechanisms.
title_fullStr Neisseria gonorrhoeae infects the heterogeneous epithelia of the human cervix using distinct mechanisms.
title_full_unstemmed Neisseria gonorrhoeae infects the heterogeneous epithelia of the human cervix using distinct mechanisms.
title_short Neisseria gonorrhoeae infects the heterogeneous epithelia of the human cervix using distinct mechanisms.
title_sort neisseria gonorrhoeae infects the heterogeneous epithelia of the human cervix using distinct mechanisms
url https://doi.org/10.1371/journal.ppat.1008136
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