HIV, asymptomatic STI, and the rectal mucosal immune environment among young men who have sex with men

• Type of Material: Article
• Authors: Vanessa M Van Doren, Emory University; Stacey Smith, Emory University; Yijuan Hu, Emory University; Gregory A Tharp, Emory University; Steven Bosinger, Emory University; Cassie G Ackerley, Emory University; Philip R Murray, Emory University; Rama Amara, Emory University; Praveen R Amancha, Emory University; Robert C Arthur, Emory University; Richard H Johnston, Emory University; Colleen Kelley, Emory University
• Language: English
• Date: 2023-05-01
• Publisher: PUBLIC LIBRARY SCIENCE
• Publication Version: Final Published Version
• Copyright Statement: © 2023 Van Doren et al
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.ppat.1011219
• Title of Journal or Parent Work: PLOS PATHOGENS
• Volume: 19
• Issue: 5
• Start Page: e1011219
• End Page: e1011219
• Grant/Funding Information: This work was supported by the National Institutes of Health: R01AI128799 (CFK), R01HD092033 (CFK), P30AI050409, P51OD011132. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
• Keywords: Microbiology; LAMINA PROPRIA; Science & Technology; INFLAMMATION; ENRICHMENT; RESPONSES; Parasitology; CHLAMYDIA; Life Sciences & Biomedicine; T-CELLS; SEXUALLY-TRANSMITTED INFECTIONS; RISK-FACTORS; GUT MICROBIOTA; REPLICATION; Virology
• Research Categories: Biology, Bioinformatics; Biology, Biostatistics

Abstract

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 18-29 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.