Binding and transfer of human immunodeficiency virus by DC-SIGN+ cells in human rectal mucosa

J Virol. 2005 May;79(9):5762-73. doi: 10.1128/JVI.79.9.5762-5773.2005.

Abstract

The role of DC-SIGN on human rectal mucosal dendritic cells is unknown. Using highly purified human rectal mucosal DC-SIGN+ cells and an ultrasensitive real-time reverse transcription-PCR assay to quantify virus binding, we found that HLA-DR+/DC-SIGN+ cells can bind and transfer more virus than the HLA-DR+/DC-SIGN- cells. Greater than 90% of the virus bound to total mucosal mononuclear cells (MMCs) was accounted for by the DC-SIGN+ cells, which comprise only 1 to 5% of total MMCs. Significantly, anti-DC-SIGN antibodies blocked 90% of the virus binding when more-physiologic amounts of virus inoculum were used. DC-SIGN expression in the rectal mucosa was significantly correlated with the interleukin-10 (IL-10)/IL-12 ratio (r = 0.58, P < 0.002; n = 26) among human immunodeficiency virus (HIV)-positive patients. Ex vivo and in vitro data implicate the role of IL-10 in upregulating DC-SIGN expression and downregulating expression of the costimulatory molecules CD80/CD86. Dendritic cells derived from monocytes (MDDCs) in the presence of IL-10 render the MDDCs less responsive to maturation stimuli, such as lipopolysaccharide and tumor necrosis factor alpha, and migration to the CCR7 ligand macrophage inflammatory protein 3beta. Thus, an increased IL-10 environment could render DC-SIGN(+) cells less immunostimulatory and migratory, thereby dampening an effective immune response. DC-SIGN and the IL-10/IL-12 axis may play significant roles in the mucosal transmission and pathogenesis of HIV type 1.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Adhesion Molecules / metabolism*
  • Cells, Cultured
  • HIV Infections / immunology*
  • HIV-1 / immunology*
  • HIV-1 / metabolism
  • HIV-1 / physiology
  • HLA-DR Antigens
  • Humans
  • Interleukin-10 / immunology
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / virology
  • Lectins, C-Type / metabolism*
  • Movement
  • Receptors, Cell Surface / metabolism*
  • T-Lymphocytes / virology
  • Up-Regulation
  • Virus Replication

Substances

  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • HLA-DR Antigens
  • Lectins, C-Type
  • Receptors, Cell Surface
  • Interleukin-10