title: Neisseria gonorrhoeae infection protects human endocervical epithelial cells from apoptosis via expression of host antiapoptotic proteins.
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-kappaB activation and resulted in increased gene expression of the NF-kappaB-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.
authors: Department of Microbiology, Section of Molecular Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors: S A
authors: SA
authors: Follows
authors: J
authors: J
authors: Murlidharan
authors: P
authors: P
authors: Massari
authors: L M
authors: LM
authors: Wetzler
authors: C A
authors: CA
authors: Genco
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000235:genetics; D053148:Caspase 3 / Q000502:physiology; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000382:microbiology* / Q000473:pathology; D005260:Female; D006069:Gonorrhea / Q000276:immunology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology; D009344:Neisseria gonorrhoeae / Q000472:pathogenicity*; D018272:Porins / Q000502:physiology; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2 / Q000235:genetics; D019311:Staurosporine / Q000494:pharmacology; D044767:Ubiquitin-Protein Ligases
chemical_list: D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D051034:Inhibitor of Apoptosis Proteins; D016328:NF-kappa B; D018272:Porins; C057699:porin protein, Neisseria; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D044767:Ubiquitin-Protein Ligases; C506253:RIPK2 protein, human; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D053148:Caspase 3; D019311:Staurosporine