title: Breast milk macrophages spontaneously produce granulocyte-macrophage colony-stimulating factor and differentiate into dendritic cells in the presence of exogenous interleukin-4 alone.
abstract: Peripheral blood monocytes extravasate and differentiate into tissue macrophages to mediate effective local defence, but how tissue-specific stimuli and environments may influence their functions remains unknown. Here, we found that peripheral blood monocytes gained the ability to produce granulocyte-macrophage colony-stimulating factor (GM-CSF) upon exposure to breast milk and differentiated into CD1+ dendritic cells (DCs) in the presence of exogenous interleukin-4 (IL-4) alone. This in vitro observation appeared physiologically relevant since macrophages that were freshly isolated from breast milk were also found to produce GM-CSF spontaneously. Furthermore, in contrast to peripheral blood monocytes that differentiated into DCs only in the presence of both exogenous GM-CSF and IL-4, differentiation of breast milk macrophages into DCs was induced by incubation with exogenous IL-4 alone. These IL-4-stimulated breast milk macrophages were efficient in stimulating T cells, suggesting their potential role in mediating T-cell-dependent immune responses in situ. On the other hand, unexpected expression of DC-SIGN, a DC-specific receptor for human immunodeficiency virus (HIV), even in unstimulated breast milk macrophages, may favour HIV infection, resulting in an increased risk of mother-to-infant vertical transmission of the virus via breast milk. Thus, tissue-specific development of macrophages is often linked to effective local immunity, but may potentially provide an opportunity for a pathogen to spread and transmit.
authors.affiliation: Department of Microbiology and Immunology, Nippon Medical School, Tokyo, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Ichikawa
authors.forename: Masahiko
authors.initials: M
authors.lastname: Sugita
authors.forename: Megumi
authors.initials: M
authors.lastname: Takahashi
authors.forename: Misao
authors.initials: M
authors.lastname: Satomi
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takeshita
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Araki
authors.forename: Hidemi
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D015815:Cell Adhesion Molecules / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D006801:Humans; D016130:Immunophenotyping; D015847:Interleukin-4 / Q000276:immunology*; D037181:Lectins, C-Type / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D008895:Milk, Human / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015847:Interleukin-4; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin