Lewis X component in human milk binds DC-SIGN and inhibits HIV-1 transfer to CD4+ T lymphocytes.
DC-specific ICAM3-grabbing non-integrin (DC-SIGN), which is expressed on DCs, can interact with a variety of pathogens such as HIV-1, hepatitis C, Ebola, cytomegalovirus, Dengue virus, Mycobacterium, Leishmania, and Candida albicans. We demonstrate that human milk can inhibit the DC-SIGN-mediated transfer of HIV-1 to CD4+ T lymphocytes as well as viral transfer by both immature and mature DCs. The inhibitory factor directly interacted with DC-SIGN and prevented the HIV-1 gp120 envelope protein from binding to the receptor. The human milk proteins lactoferrin, alpha-lactalbumin, lysozyme, beta-casein, and secretory leukocyte protease inhibitor did not bind DC-SIGN or demonstrate inhibition of viral transfer. The inhibitory effect could be fully alleviated with an Ab recognizing the Lewis X (LeX) sugar epitope, commonly found in human milk. LeX in polymeric form or conjugated to protein could mimic the inhibitory activity, whereas free LeX sugar epitopes could not. We reveal that a LeX motif present in human milk can bind to DC-SIGN and thereby prevent the capture and subsequent transfer of HIV-1 to CD4+ T lymphocytes. The presence of such a DC-SIGN-binding molecule in human milk may both influence antigenic presentation and interfere with pathogen transfer in breastfed infants.
Naarding
Marloes A
MA
Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Ludwig
Irene S
IS
Groot
Fedde
F
Berkhout
Ben
B
Geijtenbeek
Teunis B H
TB
Pollakis
Georgios
G
Paxton
William A
WA
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D015815:Cell Adhesion Molecules / Q000378:metabolism* / Q000502:physiology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control* / Q000635:transmission; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D037181:Lectins, C-Type / Q000378:metabolism* / Q000502:physiology; D016256:Lewis X Antigen / Q000378:metabolism* / Q000502:physiology / Q000031:analogs & derivatives; D008895:Milk, Human / Q000276:immunology* / Q000378:metabolism*; D011485:Protein Binding / Q000276:immunology; D011956:Receptors, Cell Surface / Q000378:metabolism* / Q000502:physiology; D014312:Trisaccharides / Q000378:metabolism* / Q000502:physiology; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D016256:Lewis X Antigen; D011956:Receptors, Cell Surface; D014312:Trisaccharides; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C110530:galactosyl-(1,4)-fucopyranosyl-(1,3)-N-acetylglucosamine