{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T02:45:38Z","timestamp":1772765138901,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011219","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T00:00:00Z","timestamp":1686268800000}}],"reference-count":78,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T00:00:00Z","timestamp":1685404800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI128799"],"award-info":[{"award-number":["R01AI128799"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R01HD092033"],"award-info":[{"award-number":["R01HD092033"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["P30AI050409"],"award-info":[{"award-number":["P30AI050409"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["P51OD011132"],"award-info":[{"award-number":["P51OD011132"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Young men who have sex with men (YMSM) are disproportionately affected by HIV and bacterial sexually transmitted infections (STI) including gonorrhea, chlamydia, and syphilis; yet research into the immunologic effects of these infections is typically pursued in siloes. Here, we employed a syndemic approach to understand potential interactions of these infections on the rectal mucosal immune environment among YMSM. We enrolled YMSM aged 18\u201329 years with and without HIV and\/or asymptomatic bacterial STI and collected blood, rectal secretions, and rectal tissue biopsies. YMSM with HIV were on suppressive antiretroviral therapy (ART) with preserved blood CD4 cell counts. We defined 7 innate and 19 adaptive immune cell subsets by flow cytometry, the rectal mucosal transcriptome by RNAseq, and the rectal mucosal microbiome by 16S rRNA sequencing and examined the effects of HIV and STI and their interactions. We measured tissue HIV RNA viral loads among YMSM with HIV and HIV replication in rectal explant challenge experiments among YMSM without HIV. HIV, but not asymptomatic STI, was associated with profound alterations in the cellular composition of the rectal mucosa. We did not detect a difference in the microbiome composition associated with HIV, but asymptomatic bacterial STI was associated with a higher probability of presence of potentially pathogenic taxa. When examining the rectal mucosal transcriptome, there was evidence of statistical interaction; asymptomatic bacterial STI was associated with upregulation of numerous inflammatory genes and enrichment for immune response pathways among YMSM with HIV, but not YMSM without HIV. Asymptomatic bacterial STI was not associated with differences in tissue HIV RNA viral loads or in HIV replication in explant challenge experiments. Our results suggest that asymptomatic bacterial STI may contribute to inflammation particularly among YMSM with HIV, and that future research should examine potential harms and interventions to reduce the health impact of these syndemic infections.<\/jats:p>","DOI":"10.1371\/journal.ppat.1011219","type":"journal-article","created":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T13:44:06Z","timestamp":1685454246000},"page":"e1011219","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["HIV, asymptomatic STI, and the rectal mucosal immune environment among young men who have sex with men"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4165-6025","authenticated-orcid":true,"given":"Vanessa E.","family":"Van Doren","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. Abigail","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Juan","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory","family":"Tharp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Bosinger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cassie G.","family":"Ackerley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phillip M.","family":"Murray","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rama R.","family":"Amara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Praveen K.","family":"Amancha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert A.","family":"Arthur","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. Richard","family":"Johnston","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colleen F.","family":"Kelley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,5,30]]},"reference":[{"issue":"3","key":"ppat.1011219.ref001","doi-asserted-by":"crossref","first-page":"e90514","DOI":"10.1371\/journal.pone.0090514","article-title":"Understanding racial HIV\/STI disparities in black and white men who have sex with men: a multilevel approach","volume":"9","author":"PS Sullivan","year":"2014","journal-title":"PLoS One"},{"key":"ppat.1011219.ref002","unstructured":"HIV Surveillance Report 2019 [updated May 2021. https:\/\/www.cdc.gov\/hiv\/library\/reports\/hiv-surveillance.html."},{"key":"ppat.1011219.ref003","unstructured":"Sexually Transitted Disease Surveillance 2020: U.S. Department of Health and Human Services; 2020 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Gandhi","year":"2019","journal-title":"JAMA"},{"issue":"4","key":"ppat.1011219.ref007","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1093\/ije\/dyq057","article-title":"HIV transmission risk through anal intercourse: systematic review, meta-analysis and implications for HIV prevention","volume":"39","author":"RF Baggaley","year":"2010","journal-title":"Int J Epidemiol"},{"issue":"6","key":"ppat.1011219.ref008","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/nri2302","article-title":"Setting the stage: host invasion by HIV","volume":"8","author":"F Hladik","year":"2008","journal-title":"Nature Reviews Immunology"},{"key":"ppat.1011219.ref009","unstructured":"Sexually Transmitted Infections Treatment Guidelines, 2021: U.S. Department of Health and Human Services; 2021 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who have sex with men and transgender women in the Test and Treat cohort","volume":"30","author":"A Hiransuthikul","year":"2019","journal-title":"Int J STD AIDS"},{"issue":"4","key":"ppat.1011219.ref034","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1136\/sextrans-2013-051386","article-title":"Characteristics of LGV repeaters: analysis of LGV surveillance data","volume":"90","author":"M R\u00f6nn","year":"2014","journal-title":"Sex Transm Infect"},{"issue":"4","key":"ppat.1011219.ref035","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1093\/cid\/ciy966","article-title":"Soluble Urokinase Plasminogen Activator Receptor Is Predictive of Non-AIDS Events During Antiretroviral Therapy-mediated Viral Suppression","volume":"69","author":"M Hoenigl","year":"2019","journal-title":"Clin Infect Dis"},{"issue":"1","key":"ppat.1011219.ref036","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.4102\/sajhivmed.v22i1.1253","article-title":"Derangement of protein S and 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Mart\u00edn-Vicente","year":"2017","journal-title":"Front Immunol"},{"key":"ppat.1011219.ref040","doi-asserted-by":"crossref","DOI":"10.3389\/fcimb.2021.628275","article-title":"The Roles of TRIMs in Antiviral Innate Immune Signaling","volume":"11","author":"Z Shen","year":"2021","journal-title":"Frontiers in Cellular and Infection Microbiology"},{"issue":"6","key":"ppat.1011219.ref041","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1016\/j.celrep.2017.10.020","article-title":"The E3 Ubiquitin Ligase TRIM40 Attenuates Antiviral Immune Responses by Targeting MDA5 and","volume":"21","author":"C Zhao","year":"2017","journal-title":"RIG-I. 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