title: MUC1 in human milk blocks transmission of human immunodeficiency virus from dendritic cells to T cells.
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.
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands. e.saeland@vumc.nl
authors.forename: Eirikur
authors.initials: E
authors.lastname: Saeland
authors.forename: Marein A W P
authors.initials: MA
authors.lastname: de Jong
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Nabatov
authors.forename: Hakan
authors.initials: H
authors.lastname: Kalay
authors.forename: Teunis B H
authors.initials: TB
authors.lastname: Geijtenbeek
authors.forename: Yvette
authors.initials: Y
authors.lastname: van Kooyk
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology / Q000821:virology*; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D003713:Dendritic Cells / Q000502:physiology / Q000821:virology*; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000502:physiology; D015658:HIV Infections / Q000276:immunology / Q000635:transmission*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism; D016256:Lewis X Antigen / Q000276:immunology; D008895:Milk, Human / Q000378:metabolism*; D018396:Mucin-1 / Q000502:physiology*; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D015699:HIV Envelope Protein gp120; D037181:Lectins, C-Type; D016256:Lewis X Antigen; D018396:Mucin-1; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C060192:MUC1 protein, human