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Open AccessArticle

Bovine Lactoferrin Modulates Dendritic Cell Differentiation and Function

Cell Biology and Immunology Group, Wageningen University, P.O. Box 338, 6708 WD Wageningen, The Netherlands
FrieslandCampina, P.O. Box 1551, 3800 BN Amersfoort, The Netherlands
Author to whom correspondence should be addressed.
Nutrients 2018, 10(7), 848;
Received: 16 May 2018 / Revised: 19 June 2018 / Accepted: 26 June 2018 / Published: 29 June 2018
(This article belongs to the Special Issue Dairy Products)
Lactoferrin is an abundant glycoprotein in bovine milk that has immunomodulatory effects on human cells. Bovine lactoferrin (LF) binds lipopolysaccharides (LPS) with high affinity and is postulated to act via TLR4-dependent and -independent mechanisms. It has been shown that LF modulates differentiation of human monocytes into tolerogenic dendritic cells. However, in a previous study, we showed that LPS also mediates differentiation into tolerogenic dendritic cells (DC). Since LF binds LPS with high affinity, it remains to be investigated whether LF or LPS is mediating these effects. We, therefore, further investigated the LPS-independent effect of LF on differentiation of human monocytes into dendritic cells (DC). Human monocytes were isolated by magnetic cell sorting from freshly isolated PBMCs and cultured for six days in the presence of IL-4 and GM-CSF with or without LF or proteinase K treated LF to generate DC. These immature DC were stimulated for 48 h with LPS or Poly I:C + R848. Cell surface marker expression and cytokine production were measured by flow cytometry. DC differentiated in the presence of LF produced higher IL-6 and IL-8 levels during differentiation and showed a lower expression of CD1a and HLA-DR. These LFDCs showed to be hyporesponsive towards TLR ligands as shown by their semi-mature phenotype and reduced cytokine production. The effect of LF was abrogated by proteinase K treatment, showing that the functional effects of LF were not mediated by LPS contamination. Thus, LF alters DC differentiation and dampens responsiveness towards TLR ligands. This study indicates that LF can play a role in immune homeostasis in the human GI tract. View Full-Text
Keywords: bovine lactoferrin; moDC; DC differentiation; semi-mature phenotype; hyporesponsive; LPS bovine lactoferrin; moDC; DC differentiation; semi-mature phenotype; hyporesponsive; LPS
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Perdijk, O.; Van Neerven, R.J.J.; Van den Brink, E.; Savelkoul, H.F.J.; Brugman, S. Bovine Lactoferrin Modulates Dendritic Cell Differentiation and Function. Nutrients 2018, 10, 848.

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