title: Identification and characterization of bacterial vaginosis-associated pathogens using a comprehensive cervical-vaginal epithelial coculture assay.
abstract: Bacterial vaginosis (BV) is the most commonly treated female reproductive tract affliction, characterized by the displacement of healthy lactobacilli by an overgrowth of pathogenic bacteria. BV can contribute to pathogenic inflammation, preterm birth, and susceptibility to sexually transmitted infections. As the bacteria responsible for BV pathogenicity and their interactions with host immunity are not understood, we sought to evaluate the effects of BV-associated bacteria on reproductive epithelia. Here we have characterized the interaction between BV-associated bacteria and the female reproductive tract by measuring cytokine and defensin induction in three types of FRT epithelial cells following bacterial inoculation. Four BV-associated bacteria were evaluated alongside six lactobacilli for a comparative assessment. While responses differed between epithelial cell types, our model showed good agreement with clinical BV trends. We observed a distinct cytokine and human β-defensin 2 response to BV-associated bacteria, especially Atopobium vaginae, compared to most lactobacilli. One lactobacillus species, Lactobacillus vaginalis, induced an immune response similar to that elicited by BV-associated bacteria, stimulating significantly higher levels of cytokines and human β-defensin 2 than other lactobacilli. These data provide an important prioritization of BV-associated bacteria and support further characterization of reproductive bacteria and their interactions with host epithelia. Additionally, they demonstrate the distinct immune response potentials of epithelial cells from different locations along the female reproductive tract.
authors.affiliation: Department of Molecular Biology and Microbiology, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, United States of America.
authors.forename: Colleen R
authors.initials: CR
authors.lastname: Eade
authors.forename: Camila
authors.initials: C
authors.lastname: Diaz
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Wood
authors.forename: Kathryn
authors.initials: K
authors.lastname: Anastos
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Patterson
authors.forename: Phalguni
authors.initials: P
authors.lastname: Gupta
authors.forename: Amy L
authors.initials: AL
authors.lastname: Cole
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Cole
mesh_terms: D039903:Actinobacteria / Q000378:metabolism; D000704:Analysis of Variance; D018920:Coculture Techniques / Q000379:methods*; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000382:microbiology*; D005260:Female; D005836:Genitalia, Female / Q000166:cytology* / Q000382:microbiology; D054884:Host-Pathogen Interactions; D006801:Humans; D007778:Lactobacillus / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D016585:Vaginosis, Bacterial / Q000382:microbiology*; D023083:beta-Defensins / Q000378:metabolism
chemical_list: D016207:Cytokines; C106641:DEFB4A protein, human; D023083:beta-Defensins