Neisseria gonorrhoeae Infection Protects Human Endocervical Epithelial Cells from Apoptosis via Expression of Host Antiapoptotic Proteins

Author:

Follows S. A.1,Murlidharan J.1,Massari P.2,Wetzler L. M.12,Genco C. A.13

Affiliation:

1. Department of Microbiology

2. Department of Medicine, Section of Infectious Diseases

3. Section of Molecular Medicine, Boston University School of Medicine, 650 Albany St., Boston, Massachusetts 02118

Abstract

ABSTRACT Several microbial pathogens can modulate the host apoptotic response to infection, which may contribute to immune evasion. Various studies have reported that infection with the sexually transmitted disease pathogen Neisseria gonorrhoeae can either inhibit or induce apoptosis. N. gonorrhoeae infection initiates at the mucosal epithelium, and in women, cells from the ectocervix and endocervix are among the first host cells encountered by this pathogen. In this study, we defined the antiapoptotic effect of N. gonorrhoeae infection in human endocervical epithelial cells (End/E6E7 cells). We first established that N. gonorrhoeae strain FA1090B failed to induce cell death in End/E6E7 cells. Subsequently, we demonstrated that stimulation with N. gonorrhoeae protected these cells from staurosporine (STS)-induced apoptosis. Importantly, only End/E6E7 cells incubated with live bacteria and in direct association with N. gonorrhoeae were protected from STS-induced apoptosis, while heat-killed and antibiotic-killed bacteria failed to induce protection. Stimulation of End/E6E7 cells with live N. gonorrhoeae induced NF-κB activation and resulted in increased gene expression of the NF-κB-regulated antiapoptotic genes bfl-1 , cIAP-2 , and c-FLIP . Furthermore, cIAP-2 protein levels also increased in End/E6E7 cells incubated with gonococci. Collectively, our results indicate that the antiapoptotic effect of N. gonorrhoeae in human endocervical epithelial cells results from live infection via expression of host antiapoptotic proteins. Securing an intracellular niche through the inhibition of apoptosis may be an important mechanism utilized by N. gonorrhoeae for microbial survival and immune evasion in cervical epithelial cells.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Immunology,Microbiology,Parasitology

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1. Mechanisms of host manipulation by Neisseria gonorrhoeae;Frontiers in Microbiology;2023-02-03

2. In Vitro and in Vivo Models for Pathogenic Neisseria gonorrhoeae Infections;Research Anthology on Advancements in Women's Health and Reproductive Rights;2022-05-06

3. Bacteria-Mediated Oncogenesis and the Underlying Molecular Intricacies: What We Know So Far;Frontiers in Oncology;2022-04-04

4. In Vitro and in Vivo Models for Pathogenic Neisseria gonorrhoeae Infections;Epidemiological Research Applications for Public Health Measurement and Intervention;2021

5. Macrophage–Neisseria gonorrhoeae Interactions: A Better Understanding of Pathogen Mechanisms of Immunomodulation;Frontiers in Immunology;2018-12-21

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