The rectal mucosa and condomless receptive anal intercourse in HIV-negative MSM: implications for HIV transmission and prevention.

• Type of Material: Article
• Authors: Colleen Kelley, Emory University; Colleen Kraft, Emory University; Tom J.B. de Man, Centers for Disease Control and Prevention; Chandni Duphare, Emory University; Hyun-Woo Lee, Emory University; Jing Yang, Emory University; Kirk Easley, Emory University; Gregory K. Tharp, Emory University; Mark Mulligan, Emory University; Patrick Sullivan, Emory University; Steven Bosinger, Emory University; Rama Rao Amara, Emory University
• Language: English
• Date: 2016-11-16
• Publisher: Nature Publishing Group
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 Society for Mucosal Immunology
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/mi.2016.97
• Title of Journal or Parent Work: Mucosal Immunology
• ISSN: 1933-0219
• Volume: 10
• Start Page: 996
• End Page: 1007
• Grant/Funding Information: K23 AI108335 (CFK), U19 AI109633 (RRA), The Emory Center for AIDS Research P30AI050409, The Atlanta Clinical and Translational Science Institute UL1TR000454.
• Keywords: TYPE-1 INFECTION; T-CELLS; SEMINAL FLUID; RNA-SEQ; GUT MICROBIOTA; FEMALE REPRODUCTIVE-TRACT; EXPRESSION; MEN; SUSCEPTIBILITY; Life Sciences & Biomedicine, Immunology; TH17 CELLS; Science & Technology
• Research Categories: Health Sciences, Public Health; Health Sciences, Epidemiology; Health Sciences, Immunology

Abstract

Most HIV transmissions among men who have sex with men (MSM), the group that accounted for 67% of new US infections in 2014, occur via exposure to the rectal mucosa. However, it is unclear how the act of condomless receptive anal intercourse (CRAI) may alter the mucosal immune environment in HIV-negative MSM. Here, we performed a comprehensive characterization of the rectal mucosal immune environment for the phenotype and production of pro-inflammatory cytokines by CD4 and CD8 T cells, global transcriptomic analyses, and the composition of microbiota in HIV-negative MSM. Our results show that compared with men who had never engaged in anal intercourse, the rectal mucosa of MSM engaging in CRAI has a distinct phenotype characterized by higher levels of Th17 cells, greater CD8+ T cell proliferation and production of pro-inflammatory cytokines, molecular signatures associated with mucosal injury and repair likely mediated by innate immune cells, and a microbiota enriched for the Prevotellaceae family. These data provide a high-resolution model of the immunological, molecular, and microbiological perturbations induced by CRAI, will have direct utility in understanding rectal HIV transmission among MSM, and will enhance the design of future biomedical prevention interventions, including candidate HIV vaccines.Mucosal Immunology advance online publication 16 November 2016. doi:10.1038/mi.2016.97.