MUC1 in human milk blocks transmission of human immunodeficiency virus from dendritic cells to T cells

Mol Immunol. 2009 Jul;46(11-12):2309-16. doi: 10.1016/j.molimm.2009.03.025. Epub 2009 Apr 29.

Abstract

Mother-to-child transmission of human immunodeficiency virus-1 (HIV-1) occurs frequently via breast-feeding. HIV-1 targets DC-SIGN+ dendritic cells (DCs) in mucosal areas that allow efficient transmission of the virus to T cells. Here, we demonstrate that the epithelial mucin MUC1, abundant in milk, efficiently bound to DC-SIGN on DC. The O-linked glycans within the mucin domain contained Lewis X structures, that were specifically recognized by the receptor. Interestingly, MUC1 prevented DC-SIGN-mediated transmission of HIV-1 from DCs to CD4+ T cells. We hypothesize that repetitive units of Lewis X, within the mucin domain, play an important role in inhibiting transmission of HIV-1 from mother to child.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / physiology
  • CD4-Positive T-Lymphocytes / virology*
  • CHO Cells
  • Cell Adhesion Molecules / immunology
  • Cell Adhesion Molecules / metabolism
  • Cricetinae
  • Cricetulus
  • Dendritic Cells / physiology
  • Dendritic Cells / virology*
  • Female
  • HIV Envelope Protein gp120 / physiology
  • HIV Infections / immunology
  • HIV Infections / transmission*
  • HIV-1 / physiology*
  • Humans
  • Infectious Disease Transmission, Vertical
  • Lectins, C-Type / immunology
  • Lectins, C-Type / metabolism
  • Lewis X Antigen / immunology
  • Milk, Human / metabolism*
  • Mucin-1 / physiology*
  • Pregnancy
  • Receptors, Cell Surface / immunology
  • Receptors, Cell Surface / metabolism

Substances

  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • HIV Envelope Protein gp120
  • Lectins, C-Type
  • Lewis X Antigen
  • MUC1 protein, human
  • Mucin-1
  • Receptors, Cell Surface