title: Bacteria in the vaginal microbiome alter the innate immune response and barrier properties of the human vaginal epithelia in a species-specific manner.
abstract: BACKGROUND
  Bacterial vaginosis increases the susceptibility to sexually transmitted infections and negatively affects women's reproductive health.
  
  
  METHODS
  To investigate host-vaginal microbiota interactions and the impact on immune barrier function, we colonized 3-dimensional (3-D) human vaginal epithelial cells with 2 predominant species of vaginal microbiota (Lactobacillus iners and Lactobacillus crispatus) or 2 prevalent bacteria associated with bacterial vaginosis (Atopobium vaginae and Prevotella bivia).
  
  
  RESULTS
  Colonization of 3-D vaginal epithelial cell aggregates with vaginal microbiota was observed with direct attachment to host cell surface with no cytotoxicity. A. vaginae infection yielded increased expression membrane-associated mucins and evoked a robust proinflammatory, immune response in 3-D vaginal epithelial cells (ie, expression of CCL20, hBD-2, interleukin 1β, interleukin 6, interleukin 8, and tumor necrosis factor α) that can negatively affect barrier function. However, P. bivia and L. crispatus did not significantly upregulate pattern-recognition receptor-signaling, mucin expression, antimicrobial peptides/defensins, or proinflammatory cytokines in 3-D vaginal epithelial cell aggregates. Notably, L. iners induced pattern-recognition receptor-signaling activity, but no change was observed in mucin expression or secretion of interleukin 6 and interleukin 8.
  
  
  CONCLUSIONS
  We identified unique species-specific immune signatures from vaginal epithelial cells elicited by colonization with commensal and bacterial vaginosis-associated bacteria. A. vaginae elicited a signature that is consistent with significant disruption of immune barrier properties, potentially resulting in enhanced susceptibility to sexually transmitted infections during bacterial vaginosis.
authors.affiliation: Human and Molecular Biology Center, Saarland University, Saarbrucken, Germany Department of Basic Medical Sciences, College of Medicine-Phoenix, University of Arizona.
authors.forename: Sylvie Y
authors.initials: SY
authors.lastname: Doerflinger
authors.affiliation: Department of Basic Medical Sciences, College of Medicine-Phoenix, University of Arizona.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Throop
authors.affiliation: Department of Basic Medical Sciences, College of Medicine-Phoenix, University of Arizona.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Herbst-Kralovetz
mesh_terms: D039903:Actinobacteria / Q000276:immunology / Q000302:isolation & purification; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology*; D004848:Epithelium / Q000276:immunology / Q000382:microbiology; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007778:Lactobacillus / Q000276:immunology* / Q000302:isolation & purification; D064307:Microbiota; D009077:Mucins / Q000235:genetics / Q000378:metabolism; D018720:Prevotella / Q000276:immunology / Q000302:isolation & purification; D012749:Sexually Transmitted Diseases / Q000276:immunology / Q000517:prevention & control; D013045:Species Specificity; D014621:Vagina / Q000166:cytology / Q000276:immunology / Q000382:microbiology*; D016585:Vaginosis, Bacterial / Q000276:immunology / Q000382:microbiology
chemical_list: D023181:Antimicrobial Cationic Peptides; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D009077:Mucins
keywords: Atopobium vaginae; Lactobacillus spp.; Prevotella bivia; antimicrobial peptides; barrier function; epithelial cell; female reproductive tract; innate immunity; mucin; sexually transmitted infection; toll-like receptor; vagina; vaginal microbiota and bacterial vaginosis