Breast milk macrophages spontaneously produce granulocyte–macrophage colony‐stimulating factor and differentiate into dendritic cells in the presence of exogenous interleukin‐4 alone

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Abstract
Summary: 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.