Gardnerella vaginalis-binding IgA in the urethra of sexually experienced males.

BACKGROUND: Genital inflammation increases HIV susceptibility and is associated with the density of pro-inflammatory anaerobes in the vagina and coronal sulcus. The penile urethra is a critical site of HIV acquisition, although correlates of urethral HIV acquisition are largely unknown. While Streptococcus mitis is a consistent component of the urethral flora, the presence of Gardnerella vaginalis has been linked with prior penile-vaginal sex and urethral inflammation. Here, we use a flow cytometry-based bacterial assay to quantify urethral IgA and IgG that bind G. vaginalis and S. mitis in a cross-sectional cohort of 45 uncircumcised Ugandan men and to evaluate their association with the urethral microbiome and local soluble immune factors. RESULTS: Urethral antibodies binding both bacterial species were readily detectable, with G. vaginalis predominantly bound by IgA, and S. mitis equivalently by IgA and IgG. Gardnerella vaginalis-binding IgA was elevated in participants with detectable urethral Gardnerella, with the latter only present in participants who reported prior penile-vaginal sex. In contrast, detectable urethral S. mitis was not associated with sexual history or levels of S. mitis-binding IgA/IgG. The time from the last penile-vaginal sex was inversely correlated with the urethral concentrations of total IgA, G. vaginalis-binding IgA, and chemokines IL-8 and MIP-1β; these inflammatory chemokines were independently associated with higher total IgA concentration, but not with G. vaginalis-binding IgA. CONCLUSIONS: This first description of microbe-binding antibodies in the penile urethra suggests that urethral colonization by Gardnerella after penile-vaginal sex specifically induces a G. vaginalis-binding IgA response. Prospective studies of the host-microbe relationship in the urethra may have implications for the development of vaccines against sexually-transmitted bacteria. Video Abstract.