title: Alteration of epithelial cell transferrin-iron homeostasis by Neisseria meningitidis and Neisseria gonorrhoeae.
abstract: Iron is an essential element for nearly all organisms. In mammals, iron is transported to body tissues by the serum glycoprotein transferrin. Transferrin-iron is internalized by binding to specific receptors followed by endocytosis. In vitro, Neisseria meningitidis and Neisseria gonorrhoeae can use iron from a variety of iron-containing compounds, including human transferrin. In vivo, transferrin is an important source of iron for N. gonorrhoeae: a mutant that is unable to bind and use transferrin-iron is unable to colonize the urethra of men or initiate disease at this site. As pathogenic Neisseria and its human host derive much of their iron from transferrin, we reasoned that a competition may exist between microbe and host epithelial cells for transferrin-iron at certain stages of infection. We therefore tested the hypothesis that N. meningitidis and N. gonorrhoeae may actively interfere with host transferrin-iron metabolism. We report that Neisseria-infected human epithelial cells have reduced levels of transferrin receptor messenger RNA and cycling transferrin receptors. The ability of infected cells to internalize transferrin receptor is also reduced. Finally, the relative distribution of surface and cycling transferrin receptors is altered in an infected cell. We conclude that Neisseria infection alters epithelial cell transferrin-iron homeostasis at multiple levels.
authors.affiliation: Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland 97201-3098, USA. bonnahr@ohsu.edu
authors.forename: R A
authors.initials: RA
authors.lastname: Bonnah
authors.forename: S W
authors.initials: SW
authors.lastname: Lee
authors.forename: B L
authors.initials: BL
authors.lastname: Vasquez
authors.forename: C A
authors.initials: CA
authors.lastname: Enns
authors.forename: M
authors.initials: M
authors.lastname: So
mesh_terms: D004847:Epithelial Cells / Q000382:microbiology*; D006069:Gonorrhea / Q000382:microbiology / Q000503:physiopathology; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008589:Meningococcal Infections / Q000382:microbiology / Q000503:physiopathology; D009344:Neisseria gonorrhoeae / Q000472:pathogenicity*; D009345:Neisseria meningitidis / Q000472:pathogenicity*; D012333:RNA, Messenger / Q000378:metabolism; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D011990:Receptors, Transferrin; D014168:Transferrin; D007501:Iron