title: Reversible deficiency of antimicrobial polypeptides in bacterial vaginosis.
abstract: Bacterial vaginosis is a common condition associated with increased risk of sexually transmitted diseases, including human immunodeficiency virus infections. In contrast, vulvovaginal candidiasis has a much weaker association with sexually transmitted diseases. We found that vaginal lavage fluid from women with bacterial vaginosis is deficient in antimicrobial polypeptides and antimicrobial activity compared to fluid from healthy women or women with vulvovaginal candidiasis. Effective treatment normalized the concentrations of antimicrobial polypeptides in both bacterial vaginosis and in vulvovaginal candidiasis, suggesting that the abnormalities were a result of the diseases. Unlike in vulvovaginal candidiasis, the neutrophil attractant chemokine interleukin-8 (IL-8) was not increased in bacterial vaginosis, accounting for low concentrations of neutrophil-derived defensins in vaginal fluid. In organotypic cultures of human vaginal epithelium containing dendritic cells, treatment with Lactobacillus jensenii, a typical vaginal resident, induced the synthesis of IL-8 mRNA and the epithelial human beta-defensin-2 mRNA, but a typical bacterial vaginosis pathogen, Gardnerella vaginalis, had no effect. When the two bacteria were combined, Gardnerella vaginalis did not interfere with the immunostimulatory effect of Lactobacillus jensenii. The loss of normal immunostimulatory flora in bacterial vaginosis is thus associated with a local deficiency of multiple innate immune factors, and this deficiency could predispose individuals to sexually transmitted diseases.
authors.affiliation: Department of Medicine, CHS 37-055, David Geffen School of Medicine, Los Angeles, CA 90095-1690, USA.
authors.forename: Erika V
authors.initials: EV
authors.lastname: Valore
authors.forename: Dorothy J
authors.initials: DJ
authors.lastname: Wiley
authors.forename: Tomas
authors.initials: T
authors.lastname: Ganz
mesh_terms: D000328:Adult; D023181:Antimicrobial Cationic Peptides / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D001826:Body Fluids / Q000276:immunology* / Q000382:microbiology; D016207:Cytokines / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D005260:Female; D006194:Gardnerella vaginalis / Q000276:immunology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016209:Interleukin-8 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D019344:Lactic Acid / Q000032:analysis; D007778:Lactobacillus / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D044364:Vaginal Douching; D016585:Vaginosis, Bacterial / Q000276:immunology*; D023083:beta-Defensins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; C106641:DEFB4A protein, human; D016209:Interleukin-8; D012333:RNA, Messenger; D023083:beta-Defensins; D019344:Lactic Acid