Gardnerella vaginalis-binding IgA in the urethra of sexually experienced males
Abstract 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. Whil...
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| Language: | English |
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BMC
2025-01-01
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| Series: | Microbiome |
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| Online Access: | https://doi.org/10.1186/s40168-024-02007-4 |
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| author | Rachel Liu R. M. Galiwango Daniel Park Sanja Huibner Maliha Aziz Aggrey Anok James Nnamutete Yahaya Isbirye John Bosco Wasswa Deo Male Godfrey Kigozi Aaron A. R. Tobian Jessica L. Prodger Cindy Liu Bryan Coburn Rupert Kaul |
| author_facet | Rachel Liu R. M. Galiwango Daniel Park Sanja Huibner Maliha Aziz Aggrey Anok James Nnamutete Yahaya Isbirye John Bosco Wasswa Deo Male Godfrey Kigozi Aaron A. R. Tobian Jessica L. Prodger Cindy Liu Bryan Coburn Rupert Kaul |
| author_sort | Rachel Liu |
| collection | DOAJ |
| description | Abstract 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 |
| format | Article |
| id | doaj-art-aaa7840c2f354f8aa9580dc9d450d543 |
| institution | Kabale University |
| issn | 2049-2618 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Microbiome |
| spelling | doaj-art-aaa7840c2f354f8aa9580dc9d450d5432025-02-02T12:33:55ZengBMCMicrobiome2049-26182025-01-0113111210.1186/s40168-024-02007-4Gardnerella vaginalis-binding IgA in the urethra of sexually experienced malesRachel Liu0R. M. Galiwango1Daniel Park2Sanja Huibner3Maliha Aziz4Aggrey Anok5James Nnamutete6Yahaya Isbirye7John Bosco Wasswa8Deo Male9Godfrey Kigozi10Aaron A. R. Tobian11Jessica L. Prodger12Cindy Liu13Bryan Coburn14Rupert Kaul15Department of Medicine, University of TorontoDepartment of Immunology, University of TorontoDepartment of Environmental and Occupational Health, Milken Institute School of Public Health, George Washington UniversityDepartment of Medicine, University of TorontoDepartment of Environmental and Occupational Health, Milken Institute School of Public Health, George Washington UniversityRakai Health Science ProgramRakai Health Science ProgramRakai Health Science ProgramRakai Health Science ProgramRakai Health Science ProgramRakai Health Science ProgramDepartment of Pathology, John Hopkins University School of MedicineDepartment of Microbiology and Immunology, Western UniversityDepartment of Environmental and Occupational Health, Milken Institute School of Public Health, George Washington UniversityDepartment of Medicine, University of TorontoDepartment of Medicine, University of TorontoAbstract 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 Abstracthttps://doi.org/10.1186/s40168-024-02007-4Genital microbiomeGenital immunologyMale genital tractMucosal antibodiesUrethral microbiomeUrethral secretions |
| spellingShingle | Rachel Liu R. M. Galiwango Daniel Park Sanja Huibner Maliha Aziz Aggrey Anok James Nnamutete Yahaya Isbirye John Bosco Wasswa Deo Male Godfrey Kigozi Aaron A. R. Tobian Jessica L. Prodger Cindy Liu Bryan Coburn Rupert Kaul Gardnerella vaginalis-binding IgA in the urethra of sexually experienced males Microbiome Genital microbiome Genital immunology Male genital tract Mucosal antibodies Urethral microbiome Urethral secretions |
| title | Gardnerella vaginalis-binding IgA in the urethra of sexually experienced males |
| title_full | Gardnerella vaginalis-binding IgA in the urethra of sexually experienced males |
| title_fullStr | Gardnerella vaginalis-binding IgA in the urethra of sexually experienced males |
| title_full_unstemmed | Gardnerella vaginalis-binding IgA in the urethra of sexually experienced males |
| title_short | Gardnerella vaginalis-binding IgA in the urethra of sexually experienced males |
| title_sort | gardnerella vaginalis binding iga in the urethra of sexually experienced males |
| topic | Genital microbiome Genital immunology Male genital tract Mucosal antibodies Urethral microbiome Urethral secretions |
| url | https://doi.org/10.1186/s40168-024-02007-4 |
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