title: A co-operative interaction between Neisseria gonorrhoeae and complement receptor 3 mediates infection of primary cervical epithelial cells.
abstract: 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.
authors.affiliation: Department of Microbiology, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Edwards
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Brown
authors.forename: Sang
authors.initials: S
authors.lastname: Uk-Nham
authors.forename: Janne G
authors.initials: JG
authors.lastname: Cannon
authors.forename: Milan S
authors.initials: MS
authors.lastname: Blake
authors.forename: Michael A
authors.initials: MA
authors.lastname: Apicella
mesh_terms: D001422:Bacterial Adhesion; D001665:Binding Sites; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000166:cytology / Q000378:metabolism / Q000382:microbiology*; D003176:Complement C3 / Q000378:metabolism; D003179:Complement C3b / Q000276:immunology / Q000378:metabolism; D004705:Endocytosis; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D005260:Female; D010861:Fimbriae, Bacterial / Q000378:metabolism; D006069:Gonorrhea / Q000378:metabolism / Q000382:microbiology*; D006801:Humans; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D008954:Models, Biological; D009344:Neisseria gonorrhoeae / Q000378:metabolism / Q000472:pathogenicity*; D009895:Opsonin Proteins; D018272:Porins / Q000378:metabolism
chemical_list: D003176:Complement C3; D016177:Macrophage-1 Antigen; D009895:Opsonin Proteins; D018272:Porins; D003179:Complement C3b