title: Human Milk Blocks DC-SIGN-Pathogen Interaction via MUC1.
abstract: Beneficial effects of breastfeeding are well-recognized and include both immediate neonatal protection against pathogens and long-term protection against allergies and autoimmune diseases. Although several proteins have been identified to have anti-viral or anti-bacterial effects like secretory IgA or lactoferrin, the mechanisms of immune modulation are not fully understood. Recent studies identified important beneficial effects of glycans in human milk, such as those expressed in oligosaccharides or on glycoproteins. Glycans are recognized by the carbohydrate receptors C-type lectins on dendritic cell (DC) and specific tissue macrophages, which exert important functions in immune modulation and immune homeostasis. A well-characterized C-type lectin is dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), which binds terminal fucose. The present study shows that in human milk, MUC1 is the major milk glycoprotein that binds to the lectin domain of DC-SIGN and prevents pathogen interaction through the presence of Lewis x-type oligosaccharides. Surprisingly, this was specific for human milk, as formula, bovine or camel milk did not show any presence of proteins that interacted with DC-SIGN. The expression of DC-SIGN is found in young infants along the entire gastrointestinal tract. Our data thus suggest the importance of human milk glycoproteins for blocking pathogen interaction to DC in young children. Moreover, a potential benefit of human milk later in life in shaping the infants immune system through DC-SIGN cannot be ruled out.
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center , Amsterdam , Netherlands.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Koning
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center , Amsterdam , Netherlands.
authors.forename: Sabine F M
authors.initials: SF
authors.lastname: Kessen
authors.affiliation: Department of Pathology, VU University Medical Center , Amsterdam , Netherlands.
authors.forename: J Patrick
authors.initials: JP
authors.lastname: Van Der Voorn
authors.affiliation: Department of Medical Microbiology and Infection Control, VU University Medical Center , Amsterdam , Netherlands.
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Appelmelk
authors.affiliation: Immunology, Danone Research - Centre for Specialised Nutrition , Wageningen , Netherlands ; Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, University Utrecht , Utrecht , Netherlands.
authors.forename: Prescilla V
authors.initials: PV
authors.lastname: Jeurink
authors.affiliation: Immunology, Danone Research - Centre for Specialised Nutrition , Wageningen , Netherlands ; Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, University Utrecht , Utrecht , Netherlands.
authors.forename: Leon M J
authors.initials: LM
authors.lastname: Knippels
authors.affiliation: Immunology, Danone Research - Centre for Specialised Nutrition , Wageningen , Netherlands ; Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, University Utrecht , Utrecht , Netherlands.
authors.forename: Johan
authors.initials: J
authors.lastname: Garssen
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center , Amsterdam , Netherlands.
authors.forename: Yvette
authors.initials: Y
authors.lastname: Van Kooyk
keywords: DC-SIGN; human milk; immune modulation; intestine; mucin
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