title: Infection of human fallopian tube epithelial cells with Neisseria gonorrhoeae protects cells from tumor necrosis factor alpha-induced apoptosis.
abstract: Following infection with Neisseria gonorrhoeae, bacteria may ascend into the Fallopian tubes (FT) and induce salpingitis, a major cause of infertility. In the FT, interactions between mucosal epithelial cells and gonococci are pivotal events in the pathogen's infection cycle and the inflammatory response. In the current study, primary FT epithelial cells were infected in vitro with different multiplicities of infection (MOI) of Pil+ Opa+ gonococci. Bacteria showed a dose-dependent association with cells and induced the secretion of tumor necrosis factor alpha (TNF-alpha). A significant finding was that gonococcal infection (MOI = 1) induced apoptosis in approximately 30% of cells, whereas increasing numbers of bacteria (MOI = 10 to 100) did not induce apoptosis. Apoptosis was observed in only 11% of cells with associated bacteria, whereas >84% of cells with no adherent bacteria were apoptotic. TNF-alpha was a key contributor to apoptosis, since (i) culture supernatants from cells infected with gonococci (MOI = 1) induced apoptosis in naïve cultures, suggesting that a soluble factor was responsible; (ii) gonococcal infection-induced apoptosis was inhibited with anti-TNF-alpha antibodies; and (iii) the addition of exogenous TNF-alpha induced apoptosis, which was inhibited by the presence of increasing numbers of bacteria (MOI = 10 to 100). These data suggest that TNF-alpha-mediated apoptosis of FT epithelial cells is likely a primary host defense mechanism to prevent pathogen colonization. However, epithelial cell-associated gonococci have evolved a mechanism to protect the cells from undergoing TNF-alpha-mediated apoptosis, and this modulation of the host innate response may contribute to establishment of infection. Understanding the antiapoptotic mechanisms used by Neisseria gonorrhoeae will inform the pathogenesis of salpingitis and could suggest new intervention strategies for prevention and treatment of the disease.
authors.affiliation: Laboratorio de Inmunología de la Reproducción, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago, Chile.
authors.forename: Priscilla
authors.initials: P
authors.lastname: Morales
authors.forename: Paz
authors.initials: P
authors.lastname: Reyes
authors.forename: Macarena
authors.initials: M
authors.lastname: Vargas
authors.forename: Miguel
authors.initials: M
authors.lastname: Rios
authors.forename: Mónica
authors.initials: M
authors.lastname: Imarai
authors.forename: Hugo
authors.initials: H
authors.lastname: Cardenas
authors.forename: Horacio
authors.initials: H
authors.lastname: Croxatto
authors.forename: Pedro
authors.initials: P
authors.lastname: Orihuela
authors.forename: Renato
authors.initials: R
authors.lastname: Vargas
authors.forename: Juan
authors.initials: J
authors.lastname: Fuhrer
authors.forename: John E
authors.initials: JE
authors.lastname: Heckels
authors.forename: Myron
authors.initials: M
authors.lastname: Christodoulides
authors.forename: Luis
authors.initials: L
authors.lastname: Velasquez
mesh_terms: D017209:Apoptosis; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000382:microbiology / Q000473:pathology; D005187:Fallopian Tubes / Q000382:microbiology* / Q000473:pathology; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D009344:Neisseria gonorrhoeae / Q000472:pathogenicity*; D012488:Salpingitis / Q000209:etiology* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D014409:Tumor Necrosis Factor-alpha