A co‐operative interaction between Neisseria gonorrhoeae and complement receptor 3 mediates infection of primary cervical epithelial cells

• Published in: Cellular microbiology Vol. 4; no. 9; pp. 571 - 584
• Main Authors: Edwards, Jennifer L., Brown, Eric J., Uk‐Nham, Sang, Cannon, Janne G., Blake, Milan S., Apicella, Michael A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01-09-2002
• Subjects: Bacterial Adhesion; Binding Sites; Cells, Cultured; Cervix Uteri - cytology; Cervix Uteri - metabolism; Cervix Uteri - microbiology; Complement C3 - metabolism; Complement C3b - immunology; Complement C3b - metabolism; Endocytosis; Epithelial Cells - metabolism; Epithelial Cells - microbiology; Epithelial Cells - pathology; Female; Fimbriae, Bacterial - metabolism; Gonorrhea - metabolism; Gonorrhea - microbiology; Humans; Macrophage-1 Antigen - metabolism; Models, Biological; Neisseria gonorrhoeae - metabolism; Neisseria gonorrhoeae - pathogenicity; Opsonin Proteins; Porins - metabolism
• ISSN: 1462-5814; 1462-5822
• DOI: 10.1046/j.1462-5822.2002.t01-1-00215.x

Summary
Little is known about the pathogenesis of gonococcal infection within the lower female genital tract. We recently described the distribution of complement receptor 3 (CR3) on epithelia of the female genital tract. Our studies further indicate that CR3‐mediated endocytosis serves as a primary mechanism by which N. gonorrhoeae elicits membrane ruffling and cellular invasion of primary, human, cervical epithelial cells. We have extended these studies to describe the nature of the gonococcus–CR3 interaction. Western Blot analysis demonstrated production of alternative pathway complement components by ecto‐ and endocervical cells which allows C3b deposition on gonococci and its rapid conversion to iC3b. Anti‐iC3b and ‐factor I antibodies significantly inhibited adherence and invasion of primary cervical cells, suggesting that iC3b covalently bound to the gonococcus serves as a primary ligand for CR3 adherence. However, gonococcal porin and pili also bound to the I‐domain of CR3 in a non‐opsonic manner. Binding of porin and pili to CR3 were required for adherence to and invasion of cervical epithelia. Collectively, these data suggest that gonococcal adherence to CR3 occurs in a co‐operative manner, which requires gonococcal iC3b‐opsonization, porin and pilus. In conjunction, these molecules facilitate targeting to and successful infection of the cervical epithelium.