Soluble Immune Mediators and Vaginal Bacteria Impact Innate Genital Mucosal Antimicrobial Activity in Young Women

Rebecca Pellett Madan

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Introduction: 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<sup>®</sup>, 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.

Original languageEnglish (US)
Pages (from-to)323-332
Number of pages10
JournalAmerican Journal of Reproductive Immunology
Volume74
Issue number4
DOIs
StatePublished - Oct 1 2015

Fingerprint

Escherichia coli
Bacteria
Placebos
Secretory Leukocyte Peptidase Inhibitor
Macrophage Inflammatory Proteins
Lactoferrin
Streptococcus agalactiae
Interleukins
Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-1
Interleukin-6
HIV
SPL7013

Keywords

  • Lactobacillus
  • Escherichia coli
  • Genital innate immunity

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Obstetrics and Gynecology
  • Reproductive Medicine

Cite this

Soluble Immune Mediators and Vaginal Bacteria Impact Innate Genital Mucosal Antimicrobial Activity in Young Women. / Pellett Madan, Rebecca.

In: American Journal of Reproductive Immunology, Vol. 74, No. 4, 01.10.2015, p. 323-332.

Research output: Contribution to journalArticle

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title = "Soluble Immune Mediators and Vaginal Bacteria Impact Innate Genital Mucosal Antimicrobial Activity in Young Women",
abstract = "Introduction: 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{\circledR}, 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.",
keywords = "Lactobacillus, Escherichia coli, Genital innate immunity",
author = "{Pellett Madan}, Rebecca and {Pellett Madan}, Rebecca and Dezzutti, {Charlene S.} and Lorna Rabe and Hillier, {Sharon L.} and Jeanne Marrazzo and Ian Mcgowan and Richardson, {Barbra A.} and Herold, {Betsy C.}",
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AU - Pellett Madan, Rebecca

AU - Pellett Madan, Rebecca

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AU - Rabe, Lorna

AU - Hillier, Sharon L.

AU - Marrazzo, Jeanne

AU - Mcgowan, Ian

AU - Richardson, Barbra A.

AU - Herold, Betsy C.

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N2 - Introduction: 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.

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