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Soluble Immune Mediators and Vaginal Bacteria Impact Innate Genital Mucosal Antimicrobial Activity in Young Women
Author(s) -
Pellett Madan Rebecca,
Dezzutti Charlene S.,
Rabe Lorna,
Hillier Sharon L.,
Marrazzo Jeanne,
McGowan Ian,
Richardson Barbra A.,
Herold Betsy C.
Publication year - 2015
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/aji.12412
Subject(s) - lactoferrin , escherichia coli , microbiology and biotechnology , slpi , immune system , biology , bacteria , antimicrobial , innate immune system , immunology , vaginal flora , pathogenic bacteria , beta defensin , inflammation , bacterial vaginosis , biochemistry , genetics , gene
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.