title: The rectal mucosa and condomless receptive anal intercourse in HIV-negative MSM: implications for HIV transmission and prevention.
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.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.|Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
authors.forename: C F
authors.initials: CF
authors.lastname: Kelley
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.|Department of Pathology, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Kraft
authors.affiliation: Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: T Jb
authors.initials: TJ
authors.lastname: de Man
authors.affiliation: Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
authors.forename: C
authors.initials: C
authors.lastname: Duphare
authors.affiliation: Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
authors.forename: H-W
authors.initials: HW
authors.lastname: Lee
authors.affiliation: Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Easley
authors.affiliation: Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
authors.forename: G K
authors.initials: GK
authors.lastname: Tharp
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Mulligan
authors.affiliation: Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
authors.forename: P S
authors.initials: PS
authors.lastname: Sullivan
authors.affiliation: Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Bosinger
authors.affiliation: Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.|Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: R R
authors.initials: RR
authors.lastname: Amara
mesh_terms: D000328:Adult; D016866:Bacteroidaceae Infections / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D017280:Condoms / Q000706:statistics & numerical data; D016207:Cytokines / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control / Q000635:transmission; D018023:HIV Seronegativity; D018451:Homosexuality, Male; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D064307:Microbiota / Q000235:genetics*; D009092:Mucous Membrane / Q000276:immunology*; D018720:Prevotella / Q000235:genetics*; D012007:Rectum / Q000473:pathology*; D012725:Sexual Behavior; D058504:Th17 Cells / Q000276:immunology*; D059467:Transcriptome; D055815:Young Adult
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators