{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T09:12:08Z","timestamp":1779095528318,"version":"3.51.4"},"posted":{"date-parts":[[2026,5,14]]},"group-title":"Immunology","reference-count":56,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Specific anaerobic species within the penile microbiome \u2013 Bacteria Associated with Seroconversion, Inflammation and Immune Cells (BASIC) \u2013 have been linked to increased HIV-1 susceptibility. These bacteria can directly disrupt epithelial integrity and are believed to increase local inflammation, resulting in an increased density of HIV-susceptible T cells in the inner foreskin. It is currently unknown whether other immune cells bearing the HIV entry receptors, CD4 and CCR5, are also elevated in individuals with a high abundance of BASIC species. Using inner foreskin tissues and penile swabs from males undergoing voluntary medical male circumcision, we performed a retrospective cross-sectional study to assess the relationship between BASIC species and the tissue density of such immune cells, including CD68+ macrophages, CD11c+ dendritic cells, and CD207+ Langerhans cells.<\/jats:p>\n                <jats:p>The most abundant cells in the inner foreskin expressing the HIV co-receptors were CD11c+ dendritic cells (48.6% of CD4+\/CCR5+ cells), followed by CD68+ macrophages (28.6%), CD3+ T cells (18.8%), and CD207+ Langerhans-like (8.8%) cells. The absolute abundance of BASIC species was associated with elevated tissue densities of both CD4+\/CCR5+ T cells (as previously reported) and a heterogeneous population of CD3-\/CD4+\/CCR5+ cells of myeloid origin. In the dermis, BASIC species abundance was linked to elevated densities of cells expressing CD11c, CD68, and CD207, as well as those co-expressing CD11c and CD207; furthermore, CD11c+ and CD207+ cells were farther from the basement membrane in participants with a high abundance of BASIC species. Myeloid cells were not elevated in participants with a high abundance of control taxa. In an integrated analysis including previously published data from this same cohort, myeloid-cell densities clustered tightly together, positively correlated with BASIC species and pro-inflammatory cytokines, and had trends to negative correlations with control taxa (significant for CD207+ cell density).<\/jats:p>\n                <jats:p>Overall, our findings suggest that BASIC species are associated with a broader foreskin immune phenotype marked by increased densities of HIV-susceptible myeloid and T cells, alongside epithelial disruption.<\/jats:p>","DOI":"10.64898\/2026.05.11.724468","type":"posted-content","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T15:45:17Z","timestamp":1778773517000},"source":"Crossref","is-referenced-by-count":0,"title":["CD11c+ myeloid cells are the predominant CD4+CCR5+ immune population in the foreskin and are increased in men with HIV-associated penile anaerobes"],"prefix":"10.64898","author":[{"given":"Lane B","family":"Buchanan","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yazan","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge R","family":"Vargas","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada"},{"name":"Department of Biology, Faculty of Science, Western University, London, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongtian","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria Menya","family":"Biribawa","sequence":"additional","affiliation":[{"name":"Uganda Virus Research Institute \u2013 International AIDS Vaccine Initiative, Entebbe, Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry Rogers","family":"Ssemunywa","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada"},{"name":"Uganda Virus Research Institute \u2013 International AIDS Vaccine Initiative, Entebbe, Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annemarie","family":"Namuniina","sequence":"additional","affiliation":[{"name":"Uganda Virus Research Institute \u2013 International AIDS Vaccine Initiative, Entebbe, Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brenda","family":"Okech","sequence":"additional","affiliation":[{"name":"Uganda Virus Research Institute \u2013 International AIDS Vaccine Initiative, Entebbe, Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aaron AR","family":"Tobian","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel E","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, Milken Institute School of Public Health, George Washington University, Washington DC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cindy M","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, Milken Institute School of Public Health, George Washington University, Washington DC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rupert","family":"Kaul","sequence":"additional","affiliation":[{"name":"Department of Medicine, University Health Network, Toronto, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald M","family":"Galiwango","sequence":"additional","affiliation":[{"name":"Rakai Health Sciences Program, Rakai, Uganda"},{"name":"Department of Medicine, University Health Network, Toronto, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0805-4196","authenticated-orcid":false,"given":"Jessica L","family":"Prodger","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada"},{"name":"Department of Epidemiology and Biostatistics, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026051801550645000_2026.05.11.724468v1.1","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/S0140-6736(07)60313-4","article-title":"Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised trial","volume":"369","year":"2007","journal-title":"Lancet Lond. Engl."},{"key":"2026051801550645000_2026.05.11.724468v1.2","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/S0140-6736(07)60312-2","article-title":"Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial","volume":"369","year":"2007","journal-title":"Lancet Lond. Engl."},{"key":"2026051801550645000_2026.05.11.724468v1.3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0020298"},{"key":"2026051801550645000_2026.05.11.724468v1.4","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00076-13"},{"key":"2026051801550645000_2026.05.11.724468v1.5","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.00996-17"},{"key":"2026051801550645000_2026.05.11.724468v1.6","doi-asserted-by":"crossref","unstructured":"Prodger, J. L. et al. Penile bacteria associated with HIV seroconversion, inflammation, and immune cells. JCI Insight 6, (2021).","DOI":"10.1172\/jci.insight.147363"},{"key":"2026051801550645000_2026.05.11.724468v1.7","doi-asserted-by":"crossref","unstructured":"Galiwango, R. M. et al. Impact of antimicrobials on penile HIV susceptibility and immunology in uncircumcised men: A randomized phase 1\/2 clinical trial. Cell Rep. Med. 5, (2024).","DOI":"10.2139\/ssrn.4722048"},{"key":"2026051801550645000_2026.05.11.724468v1.8","doi-asserted-by":"crossref","first-page":"e1013094","DOI":"10.1371\/journal.ppat.1013094","article-title":"HIV-associated penile anaerobes disrupt epithelial barrier integrity","volume":"21","year":"2025","journal-title":"PLOS Pathog"},{"key":"2026051801550645000_2026.05.11.724468v1.9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1407466112"},{"key":"2026051801550645000_2026.05.11.724468v1.10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006025"},{"key":"2026051801550645000_2026.05.11.724468v1.11","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1093\/cid\/civ298","article-title":"Genital Inflammation and the Risk of HIV Acquisition in Women","volume":"61","year":"2015","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am"},{"key":"2026051801550645000_2026.05.11.724468v1.12","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4506"},{"key":"2026051801550645000_2026.05.11.724468v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.04.019"},{"key":"2026051801550645000_2026.05.11.724468v1.14","doi-asserted-by":"crossref","first-page":"e152930","DOI":"10.1172\/JCI152930","article-title":"Metronidazole treatment rapidly reduces genital inflammation through effects on bacterial vaginosis-associated bacteria rather than lactobacilli","volume":"132","year":"2022","journal-title":"J. Clin. Invest"},{"key":"2026051801550645000_2026.05.11.724468v1.15","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0000000000000232"},{"key":"2026051801550645000_2026.05.11.724468v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.03.005"},{"key":"2026051801550645000_2026.05.11.724468v1.17","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1097\/01.aids.0000237364.11123.98","article-title":"Potential HIV-1 target cells in the human penis","volume":"20","year":"2006","journal-title":"AIDS Lond. Engl"},{"key":"2026051801550645000_2026.05.11.724468v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80694-7"},{"key":"2026051801550645000_2026.05.11.724468v1.19","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10697-w"},{"key":"2026051801550645000_2026.05.11.724468v1.20","doi-asserted-by":"publisher","DOI":"10.1309\/JVHQVDJDYKM58EPH"},{"key":"2026051801550645000_2026.05.11.724468v1.21","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.090926"},{"key":"2026051801550645000_2026.05.11.724468v1.22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004440"},{"key":"2026051801550645000_2026.05.11.724468v1.23","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.05615-11"},{"key":"2026051801550645000_2026.05.11.724468v1.24","doi-asserted-by":"publisher","DOI":"10.1172\/JCI98943"},{"key":"2026051801550645000_2026.05.11.724468v1.25","doi-asserted-by":"crossref","unstructured":"Galiwango, R. M. et al. Protocol for a randomized clinical trial exploring the effect of antimicrobial agents on the penile microbiota, immunology and HIV susceptibility of Ugandan men. Trials 20, 443 (2019).","DOI":"10.1186\/s13063-019-3545-7"},{"key":"2026051801550645000_2026.05.11.724468v1.26","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/978-1-0716-2051-9_9","article-title":"Quantitative Immunofluorescent Imaging of Immune Cells in Mucosal Tissues","volume":"2440","year":"2022","journal-title":"Methods Mol. Biol. Clifton NJ"},{"key":"2026051801550645000_2026.05.11.724468v1.27","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1038\/s41598-024-52613-3","article-title":"Comparison between a deep-learning and a pixel-based approach for the automated quantification of HIV target cells in foreskin tissue","volume":"14","year":"2024","journal-title":"Sci. Rep"},{"key":"2026051801550645000_2026.05.11.724468v1.28","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-00934-2_30"},{"key":"2026051801550645000_2026.05.11.724468v1.29","doi-asserted-by":"publisher","DOI":"10.1101\/2020.10.27.357640"},{"key":"2026051801550645000_2026.05.11.724468v1.30","unstructured":"shortest distances. at <https:\/\/microscopynotes.com\/imagej\/shortest_distance_to_line\/index.html>"},{"key":"2026051801550645000_2026.05.11.724468v1.31","unstructured":"R Core Team (2021). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. https:\/\/www.R-project.org\/."},{"key":"2026051801550645000_2026.05.11.724468v1.32","unstructured":"Pipe-Friendly Framework for Basic Statistical Tests \u2022 rstatix. at <https:\/\/rpkgs.datanovia.com\/rstatix\/>"},{"key":"2026051801550645000_2026.05.11.724468v1.33","unstructured":"Create Elegant Data Visualisations Using the Grammar of Graphics. at <https:\/\/ggplot2.tidyverse.org\/>"},{"key":"2026051801550645000_2026.05.11.724468v1.34","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00766-14"},{"key":"2026051801550645000_2026.05.11.724468v1.35","doi-asserted-by":"publisher","DOI":"10.1038\/nm1297-1369"},{"key":"2026051801550645000_2026.05.11.724468v1.36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004729"},{"key":"2026051801550645000_2026.05.11.724468v1.37","doi-asserted-by":"crossref","first-page":"e108954","DOI":"10.1371\/journal.pone.0108954","article-title":"The Inner Foreskin of Healthy Males at Risk of HIV Infection Harbors Epithelial CD4+ CCR5+ Cells and Has Features of an Inflamed Epidermal Barrier","volume":"9","year":"2014","journal-title":"PLoS ONE"},{"key":"2026051801550645000_2026.05.11.724468v1.38","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64247-2"},{"key":"2026051801550645000_2026.05.11.724468v1.39","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1097\/QAD.0b013e328321b778","article-title":"HIV-1 infection of human penile explant tissue and protection by candidate microbicides","volume":"23","year":"2009","journal-title":"AIDS Lond. Engl"},{"key":"2026051801550645000_2026.05.11.724468v1.40","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2010.32"},{"key":"2026051801550645000_2026.05.11.724468v1.41","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002100"},{"key":"2026051801550645000_2026.05.11.724468v1.42","doi-asserted-by":"crossref","first-page":"e0070721","DOI":"10.1128\/JVI.00707-21","article-title":"Th17 T Cells and Immature Dendritic Cells Are the Preferential Initial Targets after Rectal Challenge with a Simian Immunodeficiency Virus-Based Replication-Defective Dual-Reporter Vector","volume":"95","year":"2021","journal-title":"J. Virol."},{"key":"2026051801550645000_2026.05.11.724468v1.43","doi-asserted-by":"crossref","first-page":"e1013490","DOI":"10.1371\/journal.ppat.1013490","article-title":"Dendritic cells and HIV transmission: roles and subsets of antigen-presenting cells in the human anogenital tract","volume":"21","year":"2025","journal-title":"PLOS Pathog"},{"key":"2026051801550645000_2026.05.11.724468v1.44","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2010.18"},{"key":"2026051801550645000_2026.05.11.724468v1.45","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0191524"},{"key":"2026051801550645000_2026.05.11.724468v1.46","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01377-13"},{"key":"2026051801550645000_2026.05.11.724468v1.47","doi-asserted-by":"crossref","first-page":"103648","DOI":"10.1016\/j.jri.2022.103648","article-title":"Gardnerella vaginalis induces matrix metalloproteinases in the cervicovaginal epithelium through TLR-2 activation","volume":"152","year":"2022","journal-title":"J. Reprod. Immunol"},{"key":"2026051801550645000_2026.05.11.724468v1.48","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/s41522-021-00259-8","article-title":"Bacterial vaginosis and health-associated bacteria modulate the immunometabolic landscape in 3D model of human cervix","volume":"7","year":"2021","journal-title":"NPJ Biofilms Microbiomes"},{"key":"2026051801550645000_2026.05.11.724468v1.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.01.007"},{"key":"2026051801550645000_2026.05.11.724468v1.50","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.21.12607"},{"key":"2026051801550645000_2026.05.11.724468v1.51","doi-asserted-by":"publisher","DOI":"10.1084\/jem.176.5.1375"},{"key":"2026051801550645000_2026.05.11.724468v1.52","first-page":"3369","article-title":"IL-8 directly enhanced endothelial cell survival, proliferation, and matrix metalloproteinases production and regulated angiogenesis","volume":"170","year":"2003","journal-title":"J. Immunol. Baltim. Md"},{"key":"2026051801550645000_2026.05.11.724468v1.53","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(02)00259-5"},{"key":"2026051801550645000_2026.05.11.724468v1.54","doi-asserted-by":"crossref","first-page":"3283","DOI":"10.1038\/s41598-023-30097-x","article-title":"Immune activation of vaginal human Langerhans cells increases susceptibility to HIV-1 infection","volume":"13","year":"2023","journal-title":"Sci. Rep"},{"key":"2026051801550645000_2026.05.11.724468v1.55","doi-asserted-by":"crossref","first-page":"e435","DOI":"10.1016\/S2666-5247(22)00043-X","article-title":"Sustained effect of LACTIN-V (Lactobacillus crispatus CTV-05) on genital immunology following standard bacterial vaginosis treatment: results from a randomised, placebo-controlled trial","volume":"3","year":"2022","journal-title":"Lancet Microbe"},{"key":"2026051801550645000_2026.05.11.724468v1.56","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-11-058438"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.05.11.724468","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T08:55:19Z","timestamp":1779094519000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.05.11.724468"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,14]]},"references-count":56,"URL":"https:\/\/doi.org\/10.64898\/2026.05.11.724468","relation":{},"subject":[],"published":{"date-parts":[[2026,5,14]]},"subtype":"preprint"}}