Invasion of human mucosal epithelial cells by Neisseria gonorrhoeae upregulates expression of intercellular adhesion molecule 1 (ICAM-1)

Infection of the mucosa by Neisseria gonorrhoeae involves adherence to and invasion of epithelial cells. Little is known, however, about the expressio n by mucosal epithelial cells of molecules that mediate cellular interactio ns between epithelial cells and neutrophils at the site of gonococcal infec tion, The aim of this study was to determine the expression of intercellula r adhesion molecule I (ICAM-1) by epithelial cells during the process of go nococcal invasion. The highly invasive strain FA1090 and the poorly invasiv e strain MS11 were incubated with human endometrial adenocarcinoma (HEC-1-B ) or human cervical carcinoma (ME-180) epithelial cells, after which ICAM-1 expression was measured by flow cytometry, After 15 h of infection with FA 1090, expression of ICAM-1 increased 4.7- and 2.1-fold for HEC-1-B and ME-1 80 cells, respectively, whereas 15 h of infection of HEC-1-B cells with MS1 1 increased ICAM-1 expression only 1.6-fold. ICAM-1 expression was restrict ed to the cell surface, since no soluble ICAM-1 was detected. The distribut ion of staining was heterogeneous and mimicked that seen after treatment of HEC-1-B cells with the ICAM-1 agonist tumor necrosis factor alpha (TNF-alp ha) in the absence of bacteria. PCR and dot blot analyses of ICAM-1 mRNA sh owed no change in levels over time in response to infection. Although TNF-o r was produced by HEC-1-B cells after infection, the extent of ICAM-1 upreg ulation was not affected by neutralizing anti-TNF-alpha antiserum. Dual-flu orescence flow cytometry showed that the cells with the highest levels of I CAM-1 expression were cells with associated gonococci. We conclude that epi thelial cells upregulate the expression of ICAM-1 in response to infection with invasive gonococci. On the mucosa, upregulation of ICAM-1 by infected epithelial cells may function to maintain neutrophils at the site of infect ion, thereby reducing further invasion of the mucosa by gonococci.