Ultrastructural analysis of the pathogenesis of Neisseria gonorrhoeae endometrial infection

Abstract

SummaryWe have studied gonococcal infection in human endometrium organ culture and in human primary endometrial epithelial cells using various microscopic techniques including scanning electron microscopy, transmission electron microscopy, bright field light microscopy and laser scanning confocal microscopy. Here we describe the interactions between Neisseria gonorrhoeae and human endometrial luminal epithelial cells at the ultrastructural levels. N. gonorrhoeae attached to cilia but were not observed associated with the plasma membrane of ciliated epithelial cells or internalized into ciliated epithelial cells. N. gonorrhoeae could be found in intracellular vacuoles in secretory epithelial cells. N. gonorrhoeae have diverse interactions with endometrial epithelium. These include intimate association and colocalization with asialoglycoprotein receptor (ASGP-R) and CEACAM, lamellipodia and ruffle formation and colocalization with CR3, and microvillus engagement. These studies indicate that N. gonorrhoeae utilize multiple mechanisms to associate with endometrial epithelial cells and can associate with both ciliated and secretory cells. This diversity is consistent with a role of the endometrium as a transition zone between frequently asymptomatic cervical gonorrhoea and symptomatic pelvic inflammatory disease.

The cell surface environment for pathogen recognition and entry

“…Other bacteria such as Yersinia spp. and Neisseria gonorrhoeae induce plasma membrane ruffling to gain entry to host cells 75 , 76 . Additional bacterial effectors hijack cell signalling and the maturation of macropinosomes to avoid detection and destruction, creating protective vacuoles inside host cells for sequestration and proliferation.…”

The Biology of Neisseria Adhesins

“…Gonococcal pili and Opa co-operate during adherence to and invasion of HEC-1B cells [282]. This co-operative interaction was reported to co-localise with ASPG-R and CEACAM receptors on epithelial cells of the endometrium [283], suggesting that expression of these host cell receptors is possibly important for ascending infection. In addition, OmpA protein has been shown to mediate gonococcal adhesion to human cervical carcinoma and endometrial epithelial cells in vitro [139].…”

The Pathobiology of Neisseria gonorrhoeae Lower Female Genital Tract Infection

“…Although the ASGP-R is present within the female genital tract, it does not appear to mediate gonococcal infection of pex cells. However, the co-localization of gonococci with the ASGP-R on endometrial epithelium (Timmerman et al, 2005) could indicate that the ASGP-R plays a role in ascending infection in women. Challenge of ME-180 (omentum metastatic cervical epidermoid carcinoma) cells with a panel of LOS truncation mutants show adherence and invasion comparable to that of the wildtype strain (Minor et al, 2000).…”

“…The expression of CEACAMs on the mucosal surface of the female genital tract increases from the cervix to the fallopian tubes. Gonococci co-localize with CEACAMs on the luminal face of endometrial tissue (Timmerman et al, 2005). These data hint at a role for a CEACAM–gonococcus interaction in augment ascending infection in women; however, further studies to elucidate how ascending infection may progress in women are needed.…”