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

Record type: Article

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.

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Citation

Morales, Priscilla, Reyes, Paz, Vargas, Macarena, Rios, Miguel, Imarai, Mónica, Cardenas, Hugo, Croxatto, Horacio, Orihuela, Pedro, Vargas, Renato, Fuhrer, Juan, Heckels, John E., Christodoulides, Myron and Velasquez, Luis (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), pp. 3643-3650. (doi:10.1128/IAI.00012-06).

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Published date: June 2006

Identifiers

Local EPrints ID: 59378
URI: http://eprints.soton.ac.uk/id/eprint/59378
ISSN: 0019-9567
PURE UUID: 03086199-13c5-4708-99c6-27a037c33568

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Date deposited: 03 Sep 2008
Last modified: 17 Jul 2017 14:24

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Contributors

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

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