Inhibition of DC-SIGN-mediated Trans Infection of T Cells by Mannose-Binding Lectin

Immunology. 2003 Sep;110(1):80-5. doi: 10.1046/j.1365-2567.2003.01707.x.

Abstract

Some dendritic cells (DC) express a cell-surface lectin called 'dendritic cell-specific intracellular adhesion molecule 3 (ICAM-3)-grabbing non-integrin' (DC-SIGN). DC-SIGN has been shown to mediate a type of infection called 'trans' infection, where DC bind human immunodeficiency virus (HIV) and efficiently transfer the virus to T cells. We investigated the possibility that mannose-binding lectin (MBL), a soluble lectin that functions as a recognition molecule in innate immunity and that binds to HIV, could block trans infection mediated by DC-SIGN. Binding studies with glycoprotein (gp)120/gp41-positive and -negative virus preparations suggested that DC-SIGN and MBL bind primarily to glycans on gp120/gp41, as opposed to glycans on host-cell-derived proteins, indicating a close overlap in the binding site of the two lectins and supporting the notion that MBL could prevent binding of HIV to DC-SIGN. Preincubation of X4, R5 or dual-tropic HIV strains with MBL prevented DC-SIGN-mediated trans infection of T cells. The mechanism of MBL blocking trans infection of T cells was at least partly caused by blocking of virus binding to DC-SIGN positive cells. This study shows that MBL prevents DC-SIGN-mediated trans infection of T cells in vitro and suggests that in infected persons, MBL may inhibit DC-SIGN-mediated uptake and spread of HIV.

Publication types

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

MeSH terms

  • Binding, Competitive
  • Cell Adhesion Molecules / metabolism*
  • Cells, Cultured
  • Dendritic Cells / immunology
  • HIV / metabolism
  • HIV Infections / immunology*
  • HIV Infections / metabolism
  • Humans
  • Lectins, C-Type / metabolism*
  • Mannose-Binding Lectin / metabolism*
  • Receptors, Cell Surface / metabolism*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / virology*

Substances

  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • Lectins, C-Type
  • Mannose-Binding Lectin
  • Receptors, Cell Surface