Bacterial Vaginosis Is Associated With Transcriptomic Changes but Not Higher Concentrations of Cervical Leukocytes in a Study of Women at High Risk for Human Immunodeficiency Virus Acquisition
- PMID: 39874304
- PMCID: PMC12247804
- DOI: 10.1093/infdis/jiaf049
Bacterial Vaginosis Is Associated With Transcriptomic Changes but Not Higher Concentrations of Cervical Leukocytes in a Study of Women at High Risk for Human Immunodeficiency Virus Acquisition
Abstract
Background: The association between bacterial vaginosis (BV) and increased human immunodeficiency virus (HIV) acquisition risk may be related to concentrations of HIV-susceptible immune cells in the cervix.
Methods: Participants (31 with BV and 30 with normal microbiota) underwent cervical biopsy at a single visit. Immune cells were quantified and sorted using flow cytometry (n = 55), localization assessed by immunofluorescence (n = 16), and function determined by bulk RNA sequencing (RNA-seq) of live CD45+ cells (n = 21).
Results: Linear regression analyses demonstrated no differences in mean log2 (cells/mg tissue) between women with BV versus normal microbiota for antigen-presenting cell (APC) subtypes linked to HIV risk (including CD1a+HLA-DR+ Langerhans cells, CD11c+CD14+ dendritic cells [DCs], and CD11c+HLA-DR+ DCs) and CD4+ T cells. Women with BV had a higher median proportion of CD11c+HLA-DR+ APCs (out of total cells) in cervical epithelium (0.1% vs 0.0%; P = .03 using Mann-Whitney test). RNA-seq identified 1032 differentially expressed genes (adjusted P < .05) in CD45+ cells between women with BV versus normal microbiota. Women with BV demonstrated downregulation of pathways linked to translation, metabolism, cell stress, and immune signaling.
Conclusions: BV alters immune cell localization and function; future studies are needed to address how these changes may mediate HIV acquisition risk.
Keywords: HIV; bacterial vaginosis; dendritic cell; female reproductive tract; microbiome.
© The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.
Conflict of interest statement
Potential conflicts of interest. R. S. M. receives research funding and sexually transmitted infection testing supplies, paid to the University of Washington, from Hologic Corporation. B. A. R. receives honoraria from Gilead for serving on data and safety monitoring boards. D. N. F. and T. L. F. have received royalties from BD. All other authors report no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
References
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- Fredricks DN, Fiedler TL, Marrazzo JM. Molecular identification of bacteria associated with bacterial vaginosis. N Engl J Med 2005; 353:1899–911. - PubMed
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