Susceptibility to human immunodeficiency virus-1 infection of human foreskin and cervical tissue grown in explant culture

Am J Pathol. 2002 Sep;161(3):867-73. doi: 10.1016/S0002-9440(10)64247-2.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cervix Uteri / virology*
  • Circumcision, Male
  • Culture Techniques
  • Disease Susceptibility
  • Female
  • Fluorescent Antibody Technique
  • HIV Infections / etiology*
  • HIV Infections / pathology
  • HIV-1*
  • Humans
  • Male
  • Mucous Membrane / virology
  • Penis / virology*
  • Skin / virology