Neisseria gonorrhoeae elicits membrane ruffling and cytoskeletal rearrangements upon infection of primary human endocervical and ectocervical cells

Neisseria gonorrhoeae is a strict human pathogen that is, primarily, transm itted by close sexual contact with an infected individual. Gonococcal infec tion of the male urogenital tract has been well studied in experimental hum an models and in urethral cell culture systems. Recent studies, using tissu e culture cell systems, have suggested a role for the cervical epithelium i n gonococcal infection of females; however, the nature of gonococcal infect ion of the normal uterine cervix remains controversial, To address this eni gma, we have developed two primary human cervical epithelial cell systems f rom surgical biopsies. Gonococcal infection studies and electron microscopy show that N. gonorrhoeae is capable of infecting and invading both the end o- and the ectocervix. Invasion was found to occur primarily in an actin-de pendent manner, but it does not appear to require de novo protein synthesis by either the bacterium or the host cervical cell. Membrane ruffles appear to be induced in response to gonococci. Consistent with membrane ruffling, gonococci were found residing within macropinosomes, and a concentrated ac cumulation of actin-associated proteins was observed to occur in response t o gonococcal infection. Electron microscopy of clinically derived cervical biopsies show that lamellipodia formation and cytoskeletal changes, suggest ive of membrane ruffles, also occur in the cervical epithelium of women wit h naturally acquired gonococcal cervicitis. These studies demonstrate the a bility of N. gonorrhoeae to infect and invade both the endo- and the ectoce rvix of the normal uterine cervix. Gonococcal induced ruffling is a novel f inding and may be unique to the cervical epithelium.