TY - JOUR

T1 - Milk-derived GM3 and GD3 differentially inhibit dendritic cell maturation and effector functionalities

AU - Brønnum, H.

AU - Seested, T.

AU - Hellgren, L. I.

AU - Brix, S.

AU - Frøkiær, H.

PY - 2005/6

Y1 - 2005/6

N2 - Gangliosides are complex glycosphingolipids, which exert immune-modulating effects on various cell types. Ganglioside GD3 and GM3 are the predominant gangliosides of human breast milk but during the early phase of lactation, the content of GD3 decreases while GM3 increases. The biological value of gangliosides in breast milk has yet to be elucidated but when milk is ingested, dietary gangliosides might conceptually affect immune cells, such as dendritic cells (DCs). In this study, we address the in vitro effect of GD3 and GM3 on DC effector functionalities. Treatment of bone marrow-derived DCs with GD3 before lipopolysaccharide-induced maturation decreased the production of interleukin-6 (IL-6), IL-10, IL-12 and tumor necrosis factor-α as well as reduced the alloreactivity in mixed leucocyte reaction (MLR). In contrast, only IL-10 and IL-12 productions were significantly inhibited by GM3 and the potency of DCs to activate CD4+ cells in MLR was unaffected by GM 3. However, both gangliosides suppressed expression of CD40, CD80, CD86 and major histocompatibility complex class II on DCs. Because GD 3 overall inhibits DC functionalities more than GM3, the immune modulating effect of the ganglioside fraction of breast milk might be more prominent in the commencement of lactation during which the milk contains the most GD3.

AB - Gangliosides are complex glycosphingolipids, which exert immune-modulating effects on various cell types. Ganglioside GD3 and GM3 are the predominant gangliosides of human breast milk but during the early phase of lactation, the content of GD3 decreases while GM3 increases. The biological value of gangliosides in breast milk has yet to be elucidated but when milk is ingested, dietary gangliosides might conceptually affect immune cells, such as dendritic cells (DCs). In this study, we address the in vitro effect of GD3 and GM3 on DC effector functionalities. Treatment of bone marrow-derived DCs with GD3 before lipopolysaccharide-induced maturation decreased the production of interleukin-6 (IL-6), IL-10, IL-12 and tumor necrosis factor-α as well as reduced the alloreactivity in mixed leucocyte reaction (MLR). In contrast, only IL-10 and IL-12 productions were significantly inhibited by GM3 and the potency of DCs to activate CD4+ cells in MLR was unaffected by GM 3. However, both gangliosides suppressed expression of CD40, CD80, CD86 and major histocompatibility complex class II on DCs. Because GD 3 overall inhibits DC functionalities more than GM3, the immune modulating effect of the ganglioside fraction of breast milk might be more prominent in the commencement of lactation during which the milk contains the most GD3.

UR - http://www.scopus.com/inward/record.url?scp=21244472276&partnerID=8YFLogxK

U2 - 10.1111/j.1365-3083.2005.01566.x

DO - 10.1111/j.1365-3083.2005.01566.x

M3 - Journal article

C2 - 15963050

AN - SCOPUS:21244472276

VL - 61

SP - 551

EP - 557

JO - Scandinavian Journal of Immunology, Supplement

JF - Scandinavian Journal of Immunology, Supplement

SN - 0301-6323

IS - 6

ER -