IAI Accepts, published online ahead of print on 22 June 2009

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Infect. Immun. doi:10.1128/IAI.01366-08
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Neisseria gonorrhoeae Infection Protects Human Endocervical Epithelial from Apoptosis via Expression of Host Anti-Apoptotic Proteins

S. A. Follows, J. Murlidharan, P. Massari, L. M. Wetzler, and C. A. Genco^*

Department of Microbiology, Department of Medicine, Section of Infectious Diseases and Section of Molecular Medicine, Boston University School of Medicine, 650 Albany St, Boston, MA 02118, USA

^* To whom correspondence should be addressed. Email: cgenco{at}bu.edu.

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 anti-apoptotic 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 endocervical epithelial 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-B activation and resulted in increased gene expression of the NF-B-regulated, anti-apoptotic 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 anti-apoptotic effect of N. gonorrhoeae in human endocervical epithelial cells results from live infection via expression of host anti-apoptotic 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.

This article has been cited by other articles:

• Massari, P., Gunawardana, J., Liu, X., Wetzler, L. M. (2010). Meningococcal Porin PorB Prevents Cellular Apoptosis in a Toll-Like Receptor 2- and NF-{kappa}B-Independent Manner. Infect. Immun. 78: 994-1003 [Abstract] [Full Text]