title: Soluble Immune Mediators and Vaginal Bacteria Impact Innate Genital Mucosal Antimicrobial Activity in Young Women.
abstract: BACKGROUND
  Innate activity against Escherichia coli in female genital secretions may represent contributions from vaginal bacteria and host soluble immune mediators. We analyzed the relationship between E. coli inhibitory activity, soluble immune mediators, and vaginal bacteria in participants in MTN-004, a placebo-controlled trial of VivaGel(®) , a candidate product for topical HIV pre-exposure prophylaxis.
  
  
  METHODS
  Escherichia coli inhibitory activity was quantified by colony reduction assay. Endocervical concentrations of interleukin (IL)-1β, IL-6, IL-12p40, macrophage inflammatory protein (MIP)-1α, granulocyte-macrophage colony-stimulating factor (GM-CSF), lactoferrin, and secretory leukocyte protease inhibitor (SLPI) were quantified to generate a cumulative mediator score. Vaginal bacteria were characterized by quantitative cultures.
  
  
  RESULTS
  In the two placebo arms, higher soluble immune mediator score was associated with greater E. coli inhibitory activity (β = 17.49, 95% CI [12.77, 22.21] and β = 13.28, 95% CI [4.76, 21.80]). However, in the VivaGel arm, higher concentrations of E. coli (β = -3.80, 95% CI [-6.36, -1.25]) and group B Streptococcus (β = -3.91, 95% CI [-6.21, -1.60]) were associated with reduced E. coli inhibitory activity.
  
  
  CONCLUSIONS
  Both host mediators and vaginal bacteria impact E. coli inhibition in genital secretions. The relative contributions of host mediators and bacteria varied between women who used VivaGel vs placebos.
authors.affiliation: Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Pellett Madan
authors.affiliation: Magee-Womens Research Institute, Pittsburgh, PA, USA.|Department of Obstetrics, Gynecology & Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Charlene S
authors.initials: CS
authors.lastname: Dezzutti
authors.affiliation: Magee-Womens Research Institute, Pittsburgh, PA, USA.
authors.forename: Lorna
authors.initials: L
authors.lastname: Rabe
authors.affiliation: Magee-Womens Research Institute, Pittsburgh, PA, USA.|Department of Obstetrics, Gynecology & Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Hillier
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Marrazzo
authors.affiliation: Magee-Womens Research Institute, Pittsburgh, PA, USA.|Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Ian
authors.initials: I
authors.lastname: McGowan
authors.affiliation: Departments of Biostatistics and Global Health, University of Washington, Seattle, WA, USA.|Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Barbra A
authors.initials: BA
authors.lastname: Richardson
authors.affiliation: Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Betsy C
authors.initials: BC
authors.lastname: Herold
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology; D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D050091:Dendrimers / Q000494:pharmacology; D004926:Escherichia coli / Q000276:immunology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology*; D053762:Interleukin-12 Subunit p40 / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D007781:Lactoferrin / Q000276:immunology; D009092:Mucous Membrane / Q000276:immunology* / Q000382:microbiology; D011107:Polylysine / Q000494:pharmacology; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000276:immunology; D013292:Streptococcus agalactiae / Q000276:immunology*; D014621:Vagina / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000900:Anti-Bacterial Agents; D050091:Dendrimers; C508585:IL1B protein, human; C508600:IL6 protein, human; D007155:Immunologic Factors; D053762:Interleukin-12 Subunit p40; D053583:Interleukin-1beta; D015850:Interleukin-6; C493277:MAPKAP1 protein, human; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D011107:Polylysine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007781:Lactoferrin; C480351:astodrimer
keywords: Escherichia coli; Lactobacillus; genital innate immunity