Liu Rachel, Galiwango R M, Park Daniel, Huibner Sanja, Aziz Maliha, Anok Aggrey, Nnamutete James, Isbirye Yahaya, Wasswa John Bosco, Male Deo, Kigozi Godfrey, Tobian Aaron A R, Prodger Jessica L, Liu Cindy, Coburn Bryan, Kaul Rupert
Department of Medicine, University of Toronto, Toronto, Canada.
Department of Immunology, University of Toronto, Toronto, Canada.
Microbiome. 2025 Jan 29;13(1):29. doi: 10.1186/s40168-024-02007-4.
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.
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.
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.
生殖器炎症会增加感染HIV的易感性，且与阴道和冠状沟中促炎性厌氧菌的密度有关。阴茎尿道是HIV感染的关键部位，尽管尿道HIV感染的相关因素大多未知。虽然缓症链球菌是尿道菌群的一个恒定组成部分，但阴道加德纳菌的存在与先前的阴茎-阴道性行为及尿道炎症有关。在此，我们使用基于流式细胞术的细菌检测方法，对45名未行包皮环切术的乌干达男性横断面队列中的尿道IgA和IgG进行定量，这些抗体可结合阴道加德纳菌和缓症链球菌，并评估它们与尿道微生物群和局部可溶性免疫因子的关联。
两种细菌的尿道抗体均易于检测到，阴道加德纳菌主要由IgA结合，缓症链球菌由IgA和IgG等量结合。在可检测到尿道阴道加德纳菌的参与者中，结合阴道加德纳菌的IgA升高，而后者仅存在于报告有过阴茎-阴道性行为的参与者中。相比之下，可检测到的尿道缓症链球菌与性病史或结合缓症链球菌的IgA/IgG水平无关。自上次阴茎-阴道性行为后的时间与总IgA、结合阴道加德纳菌的IgA以及趋化因子IL-8和MIP-1β的尿道浓度呈负相关；这些炎性趋化因子与较高的总IgA浓度独立相关，但与结合阴道加德纳菌的IgA无关。
对阴茎尿道中微生物结合抗体的首次描述表明，阴茎-阴道性行为后阴道加德纳菌在尿道的定植会特异性诱导结合阴道加德纳菌的IgA反应。对尿道中宿主-微生物关系的前瞻性研究可能对开发预防性传播细菌的疫苗有影响。视频摘要。
