The Journal of infectious diseases · 2025
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.
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Sabo Michelle C, Mustafa Salwa, Saha Aparajita, Oyaro Brenda, Fiedler Tina L, Krueger Melissa, Fuchs Esther, Mureithi Marianne, Mandaliya Kishor, Jaoko Walter, Richardson Barbra A, Gharib Sina A, Fredricks David N, Shah Javeed A, McClelland R Scott
Аннотация
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.
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.