Bacterial vaginosis is associated with transcriptomic changes but not higher concentrations of cervical leukocytes in a study of women at high risk for HIV acquisition
The association between bacterial vaginosis (BV) and increased HIV acquisition risk may be related to concentrations of HIV-susceptible immune cells in the cervix. Participants (31 with BV and 30 with normal microbiota) underwent cervical biopsy at a single visit. Immune cells were quantified and so...
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| creator | 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 |
| description | The association between bacterial vaginosis (BV) and increased HIV acquisition risk may be related to concentrations of HIV-susceptible immune cells in the cervix.
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).
Linear regression analyses demonstrated no differences in mean log2 [cells/mg tissue] between women with BV vs 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=0.03 using Mann-Whitney testing). RNA-seq identified 1,032 differentially expressed genes (adjusted p-value |
| doi_str_mv | 10.1093/infdis/jiaf049 |
| format | Article |
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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).
Linear regression analyses demonstrated no differences in mean log2 [cells/mg tissue] between women with BV vs 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=0.03 using Mann-Whitney testing). RNA-seq identified 1,032 differentially expressed genes (adjusted p-value <0.05) in CD45+ cells between women with BV vs normal microbiota. Women with BV demonstrated downregulation of pathways linked to translation, metabolism, cell stress, and immune signaling.
BV alters immune cell localization and function; future studies are needed to address how these changes may mediate HIV acquisition risk.</description><identifier>ISSN: 1537-6613</identifier><identifier>EISSN: 1537-6613</identifier><identifier>DOI: 10.1093/infdis/jiaf049</identifier><identifier>PMID: 39874304</identifier><language>eng</language><publisher>United States</publisher><ispartof>The Journal of infectious diseases, 2025-01</ispartof><rights>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.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0002-6276-3463 ; 0000-0002-5014-6687 ; 0000-0002-5058-3166 ; 0000-0002-2997-7988 ; 0009-0000-1391-4272</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39874304$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sabo, Michelle C</creatorcontrib><creatorcontrib>Mustafa, Salwa</creatorcontrib><creatorcontrib>Saha, Aparajita</creatorcontrib><creatorcontrib>Oyaro, Brenda</creatorcontrib><creatorcontrib>Fiedler, Tina L</creatorcontrib><creatorcontrib>Krueger, Melissa</creatorcontrib><creatorcontrib>Fuchs, Esther</creatorcontrib><creatorcontrib>Mureithi, Marianne</creatorcontrib><creatorcontrib>Mandaliya, Kishor</creatorcontrib><creatorcontrib>Jaoko, Walter</creatorcontrib><creatorcontrib>Richardson, Barbra A</creatorcontrib><creatorcontrib>Gharib, Sina A</creatorcontrib><creatorcontrib>Fredricks, David N</creatorcontrib><creatorcontrib>Shah, Javeed A</creatorcontrib><creatorcontrib>McClelland, R Scott</creatorcontrib><title>Bacterial vaginosis is associated with transcriptomic changes but not higher concentrations of cervical leukocytes in a study of women at high risk for HIV acquisition</title><title>The Journal of infectious diseases</title><addtitle>J Infect Dis</addtitle><description>The association between bacterial vaginosis (BV) and increased HIV acquisition risk may be related to concentrations of HIV-susceptible immune cells in the cervix.
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).
Linear regression analyses demonstrated no differences in mean log2 [cells/mg tissue] between women with BV vs 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=0.03 using Mann-Whitney testing). RNA-seq identified 1,032 differentially expressed genes (adjusted p-value <0.05) in CD45+ cells between women with BV vs normal microbiota. Women with BV demonstrated downregulation of pathways linked to translation, metabolism, cell stress, and immune signaling.
BV alters immune cell localization and function; future studies are needed to address how these changes may mediate HIV acquisition risk.</description><issn>1537-6613</issn><issn>1537-6613</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2025</creationdate><recordtype>article</recordtype><recordid>eNpNkE1rHDEMhk1JaT7aa49Fx1w28aw_dubYhrYJBHoJvS4eW95VMmNvLE-W_UX5m52QBAoCCenRc3iF-NrIi0Z26pJSDMSX9-Si1N0HcdIYtVpY26ij_-Zjccp8L6XUyq4-iWPVtSutpD4Rzz-cr1jIDfDkNpQyE8Ncjjl7chUD7KluoRaX2Bfa1TySB791aYMM_VQh5Qpb2myxgM_JY5rZSjkx5AgeyxP52T7g9JD9oc5PlMAB1ykcXoh9HnFevDqgED9AzAWub_6C848TMb3IPouP0Q2MX976mbj79fPu6npx--f3zdX328XOWL3QwbUYjZHGBqONXJlonQkhtEpZqWyMeqm73mLbaTffO4_Ym1YjWtljs1Rn4vxVuyv5cUKu65HY4zC4hHnitWrsnLpVy25Gv72hUz9iWO8Kja4c1u_Zqn_vZ4DV</recordid><startdate>20250128</startdate><enddate>20250128</enddate><creator>Sabo, Michelle C</creator><creator>Mustafa, Salwa</creator><creator>Saha, Aparajita</creator><creator>Oyaro, Brenda</creator><creator>Fiedler, Tina L</creator><creator>Krueger, Melissa</creator><creator>Fuchs, Esther</creator><creator>Mureithi, Marianne</creator><creator>Mandaliya, Kishor</creator><creator>Jaoko, Walter</creator><creator>Richardson, Barbra A</creator><creator>Gharib, Sina A</creator><creator>Fredricks, David N</creator><creator>Shah, Javeed A</creator><creator>McClelland, R Scott</creator><scope>NPM</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-6276-3463</orcidid><orcidid>https://orcid.org/0000-0002-5014-6687</orcidid><orcidid>https://orcid.org/0000-0002-5058-3166</orcidid><orcidid>https://orcid.org/0000-0002-2997-7988</orcidid><orcidid>https://orcid.org/0009-0000-1391-4272</orcidid></search><sort><creationdate>20250128</creationdate><title>Bacterial vaginosis is associated with transcriptomic changes but not higher concentrations of cervical leukocytes in a study of women at high risk for HIV acquisition</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p564-4da8ef55056d545075f6a5ddd8336036ff4249b6e894a4509ceeb584ee60be123</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2025</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sabo, Michelle C</creatorcontrib><creatorcontrib>Mustafa, Salwa</creatorcontrib><creatorcontrib>Saha, Aparajita</creatorcontrib><creatorcontrib>Oyaro, Brenda</creatorcontrib><creatorcontrib>Fiedler, Tina L</creatorcontrib><creatorcontrib>Krueger, Melissa</creatorcontrib><creatorcontrib>Fuchs, Esther</creatorcontrib><creatorcontrib>Mureithi, Marianne</creatorcontrib><creatorcontrib>Mandaliya, Kishor</creatorcontrib><creatorcontrib>Jaoko, Walter</creatorcontrib><creatorcontrib>Richardson, Barbra A</creatorcontrib><creatorcontrib>Gharib, Sina A</creatorcontrib><creatorcontrib>Fredricks, David N</creatorcontrib><creatorcontrib>Shah, Javeed A</creatorcontrib><creatorcontrib>McClelland, R Scott</creatorcontrib><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sabo, Michelle C</au><au>Mustafa, Salwa</au><au>Saha, Aparajita</au><au>Oyaro, Brenda</au><au>Fiedler, Tina L</au><au>Krueger, Melissa</au><au>Fuchs, Esther</au><au>Mureithi, Marianne</au><au>Mandaliya, Kishor</au><au>Jaoko, Walter</au><au>Richardson, Barbra A</au><au>Gharib, Sina A</au><au>Fredricks, David N</au><au>Shah, Javeed A</au><au>McClelland, R Scott</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bacterial vaginosis is associated with transcriptomic changes but not higher concentrations of cervical leukocytes in a study of women at high risk for HIV acquisition</atitle><jtitle>The Journal of infectious diseases</jtitle><addtitle>J Infect Dis</addtitle><date>2025-01-28</date><risdate>2025</risdate><issn>1537-6613</issn><eissn>1537-6613</eissn><abstract>The association between bacterial vaginosis (BV) and increased HIV acquisition risk may be related to concentrations of HIV-susceptible immune cells in the cervix.
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).
Linear regression analyses demonstrated no differences in mean log2 [cells/mg tissue] between women with BV vs 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=0.03 using Mann-Whitney testing). RNA-seq identified 1,032 differentially expressed genes (adjusted p-value <0.05) in CD45+ cells between women with BV vs normal microbiota. Women with BV demonstrated downregulation of pathways linked to translation, metabolism, cell stress, and immune signaling.
BV alters immune cell localization and function; future studies are needed to address how these changes may mediate HIV acquisition risk.</abstract><cop>United States</cop><pmid>39874304</pmid><doi>10.1093/infdis/jiaf049</doi><orcidid>https://orcid.org/0000-0002-6276-3463</orcidid><orcidid>https://orcid.org/0000-0002-5014-6687</orcidid><orcidid>https://orcid.org/0000-0002-5058-3166</orcidid><orcidid>https://orcid.org/0000-0002-2997-7988</orcidid><orcidid>https://orcid.org/0009-0000-1391-4272</orcidid></addata></record> |
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| title | Bacterial vaginosis is associated with transcriptomic changes but not higher concentrations of cervical leukocytes in a study of women at high risk for HIV acquisition |
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