TY - JOUR
T1 - Soluble Immune Mediators and Vaginal Bacteria Impact Innate Genital Mucosal Antimicrobial Activity in Young Women
AU - on behalf of the Microbicide Trials Network Biomedical Sciences Working Group and the MTN 004 Protocol Team
AU - Pellett Madan, Rebecca
AU - Dezzutti, Charlene S.
AU - Rabe, Lorna
AU - Hillier, Sharon L.
AU - Marrazzo, Jeanne
AU - Mcgowan, Ian
AU - Richardson, Barbra A.
AU - Herold, Betsy C.
N1 - Publisher Copyright:
© 2015 John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
PY - 2015/10/1
Y1 - 2015/10/1
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.
AB - 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.
KW - Escherichia coli
KW - Genital innate immunity
KW - Lactobacillus
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U2 - 10.1111/aji.12412
DO - 10.1111/aji.12412
M3 - Article
C2 - 26118476
AN - SCOPUS:84941745360
SN - 1046-7408
VL - 74
SP - 323
EP - 332
JO - American Journal of Reproductive Immunology
JF - American Journal of Reproductive Immunology
IS - 4
ER -
