Neisseria gonorrhoeae Infects the Heterogeneous Epithelia of the Human Cervix Using Distinct Mechanisms

English version

Autoři: Qian Yu ^aff001; Liang-Chun Wang ^aff001; Sofia Di Benigno ^aff001; Scott D. Gray-Owen ^aff003; Daniel C. Stein ^aff001; Wenxia Song ^aff001
Působiště autorů: Department of Cell Biology & Molecular Genetics, University of Maryland, College Park, Maryland, United States of America ^aff001; Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, Taiwan ^aff002; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada ^aff003
Vyšlo v časopise: Neisseria gonorrhoeae Infects the Heterogeneous Epithelia of the Human Cervix Using Distinct Mechanisms. PLoS Pathog 15(12): e32767. doi:10.1371/journal.ppat.1008136
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.ppat.1008136

Souhrn

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 (Opa_CEA). Relatively high levels were detected on the luminal membrane of ecto/endocervical epithelial cells but very low levels intracellularly in TZ epithelial cells. CEACAM-Opa_CEA 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.

Klíčová slova:

Cell staining – Cytoplasmic staining – Epithelial cells – Epithelium – Molting – Scanning electron microscopy – Sexually transmitted diseases – Cervix

Zdroje

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