title: Susceptibility to human immunodeficiency virus-1 infection of human foreskin and cervical tissue grown in explant culture.
abstract: Numerous studies have indicated a protective effect of male circumcision against acquisition of human immunodeficiency virus (HIV)-1. We investigated mechanisms responsible for the possible increased HIV-1 susceptibility of human foreskin. Foreskins from eight pediatric and six adult patients with (n = 3) and without (n = 11) histories of sexually transmitted disease were evaluated. Six cervical biopsies from HIV-1-seronegative women were included as controls. CD4(+) T cells, macrophages, and Langerhans' cells (LCs) were quantified using image analysis. Cells expressing HIV-1 co-receptors CCR5 and CXCR4 were quantified using immunofluorescence and image analysis. Foreskin biopsies were infected ex vivo in organotypic culture with HIV-1. HIV-1 DNA copies in foreskin and cervical mucosal tissue were compared and the infected cell phenotype was determined. Foreskin mucosa contained higher mean proportions of CD4(+) T cells (22.4%), macrophages (2.4%), and LCs (11.5%) in adults than in children (4.9%, 0.3%, and 6.2%, respectively) or in cervical mucosa (6.2%, 1.4%, and 1.5%, respectively). The highest proportions of CD4(+) T cells and LCs occurred in patients with a history of infection. Foreskin immune cells expressed predominantly the CCR5 HIV-1 co-receptor. Adult foreskin mucosa had greater susceptibility to infection with HIV(bal) than cervical mucosa or the external surface of foreskin tissue. Circumcision likely reduces risk of HIV-1 acquisition in men by decreasing HIV-1 target cells.
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, Children's Memorial Hospital, Chicago, Illinois 60614, USA. bpatterson@childrensmemorial.org
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Patterson
authors.forename: Alan
authors.initials: A
authors.lastname: Landay
authors.forename: Joan N
authors.initials: JN
authors.lastname: Siegel
authors.forename: Zareefa
authors.initials: Z
authors.lastname: Flener
authors.forename: Dennis
authors.initials: D
authors.lastname: Pessis
authors.forename: Antonio
authors.initials: A
authors.lastname: Chaviano
authors.forename: Robert C
authors.initials: RC
authors.lastname: Bailey
mesh_terms: D002584:Cervix Uteri / Q000821:virology*; D002944:Circumcision, Male; D046508:Culture Techniques; D004198:Disease Susceptibility; D005260:Female; D005455:Fluorescent Antibody Technique; D015658:HIV Infections / Q000209:etiology* / Q000473:pathology; D015497:HIV-1; D006801:Humans; D008297:Male; D009092:Mucous Membrane / Q000821:virology; D010413:Penis / Q000821:virology*; D012867:Skin / Q000821:virology