Infection of human fallopian tube epithelial cells with Neisseria gonorrhoeae protects cells from tumor necrosis factor alpha-induced apoptosis

Priscilla Morales, Paz Reyes, Macarena Vargas, Miguel Rios, Mónica Imarai, Hugo Cardenas, Horacio Croxatto, Pedro Orihuela, Renato Vargas, Juan Fuhrer, John E. Heckels, Myron Christodoulides, Luis Velasquez

Research output: Contribution to journalArticle

36 Citations (Scopus)

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-α). 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-α 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-α antibodies; and (iii) the addition of exogenous TNF-α induced apoptosis, which was inhibited by the presence of increasing numbers of bacteria (MOI = 10 to 100). These data suggest that TNF-α-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-α-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.

Original languageEnglish
Pages (from-to)3643-3650
Number of pages8
JournalInfection and Immunity
Volume74
Issue number6
DOIs
Publication statusPublished - Jun 2006

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Infection of human fallopian tube epithelial cells with Neisseria gonorrhoeae protects cells from tumor necrosis factor alpha-induced apoptosis'. Together they form a unique fingerprint.

  • Cite this

    Morales, P., Reyes, P., Vargas, M., Rios, M., Imarai, M., Cardenas, H., Croxatto, H., Orihuela, P., Vargas, R., Fuhrer, J., Heckels, J. E., Christodoulides, M., & Velasquez, L. (2006). Infection of human fallopian tube epithelial cells with Neisseria gonorrhoeae protects cells from tumor necrosis factor alpha-induced apoptosis. Infection and Immunity, 74(6), 3643-3650. https://doi.org/10.1128/IAI.00012-06