Distinct proinflammatory host responses to Neisseria gonorrhoeae infectionin immortalized human cervical and vaginal epithelial cells

In this study we utilized immortalized morphologically and functionally dis tinct epithelial cell lines from normal human endocervix, ectocervix, and v agina to characterize gonococcal epithelial interactions pertinent to the l ower female genital tract. Piliated, but not nonpiliated, N. gonorrhoeae st rain F62 variants actively invaded these epithelial cell lines, as demonstr ated by an antibiotic protection assay and confocal microscopy. Invasion of these cells by green fluorescent protein-expressing gonococci was characte rized by colocalization of gonococci with F actin, which were initially det ected 30 min postinfection. In all three cell lines, upregulation of interl eukin 8 (IL-8) and IL-6, intercellular adhesion molecule 1 (CD54), and the nonspecific cross-reacting antigen (CD66c) were detected 4 h after infectio n with piliated and nonpiliated gonococci. Furthermore, stimulation of all three cell lines with gonococcal whole-cell lysates resulted in a similar u pregulation of IL-6 and IL-8, confirming that bacterial uptake is not essen tial for this response. Increased levels of IL-1 were first detected 8 h af ter infection with gonococci, suggesting that the earlier IL-8 and IL-6 res ponses were not mediated through the IL-1 signaling pathway. The IL-1 respo nse was limited to cultures infected with piliated gonococci and was more v igorous in the endocervical epithelial cells. The ability of gonococci to s timulate distinct proinflammatory host responses in these morphologically a nd functionally different compartments of the lower female genital tract ma y contribute directly to the inflammatory signs and symptoms characteristic of disease caused by N. gonorrhoeae.