title: Atopobium vaginae triggers an innate immune response in an in vitro model of bacterial vaginosis.
abstract: Bacterial vaginosis is the most common vaginal disorder among women of reproductive age. The pathogenesis of bacterial vaginosis is poorly understood, but is defined by a transition in the vaginal flora from the predominant Lactobacillus species to other bacterial species such as Atopobium vaginae and Gardnerella vaginalis. This change is associated with an increase in vaginal cytokine secretion. We hypothesize that vaginal epithelial cells respond to bacterial vaginosis-associated bacteria by triggering an innate immune response. We observed that vaginal epithelial cells secreted interleukin-6 and interleukin-8 in response to Atopobium vaginae and Gardnerella vaginalis, but not to Lactobacillus crispatus. Atopobium vaginae induced increased levels of interleukin-6 and interleukin-8 transcripts, as well as increased transcripts for the antimicrobial peptide beta-defensin 4. This innate immune response required live bacteria capable of protein synthesis in direct contact with vaginal epithelial cells. The response of vaginal epithelial cells was mediated by Toll-like receptor 2, required the adaptor protein MyD88, and involved activation of the NFkappaB signaling pathway. These results suggest that Atopobium vaginae stimulates an innate immune response from vaginal epithelial cells, leading to localized cytokine and defensin production, and possibly contributes to the pathogenesis of bacterial vaginosis.
authors.affiliation: Molecular and Cellular Biology Division, Medical Diagnostic Laboratories, LLC. 2439 Kuser Rd., Hamilton, NJ 08690, USA.
authors.forename: Erika K
authors.initials: EK
authors.lastname: Libby
authors.forename: Kristen E
authors.initials: KE
authors.lastname: Pascal
authors.forename: Eli
authors.initials: E
authors.lastname: Mordechai
authors.forename: Martin E
authors.initials: ME
authors.lastname: Adelson
authors.forename: Jason P
authors.initials: JP
authors.lastname: Trama
mesh_terms: D039903:Actinobacteria / Q000276:immunology*; D002460:Cell Line; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D005260:Female; D006194:Gardnerella vaginalis / Q000276:immunology; D020869:Gene Expression Profiling; D006801:Humans; D007113:Immunity, Innate; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007778:Lactobacillus / Q000276:immunology; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D051195:Toll-Like Receptor 2 / Q000276:immunology; D016585:Vaginosis, Bacterial / Q000276:immunology* / Q000382:microbiology*; D023083:beta-Defensins / Q000096:biosynthesis / Q000235:genetics
chemical_list: C106641:DEFB4A protein, human; D015850:Interleukin-6; D016209:Interleukin-8; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D012333:RNA, Messenger; D051195:Toll-Like Receptor 2; D023083:beta-Defensins