Human lactoferrin attenuates the proinflammatory response of neonatal monocyte‐derived macrophages

• Published in: Clinical and experimental immunology 2018-06, Vol.192 (3), p.315-324
• Main Authors: Wisgrill, L., Wessely, I., Spittler, A., Förster‐Waldl, E., Berger, A., Sadeghi, K.
• Format: Article
• Language: English
• Subjects: Activation; Anergy; Apoptosis; Breast milk; Cell activation; Cord blood; Cytokines; Digestive system; Gastrointestinal tract; Homeostasis; Immunomodulation; Infants; Inflammatory diseases; Intestinal microflora; Intestine; Intracellular signalling; Investigations; Lactoferrin; Lipopolysaccharides; Lipoteichoic acid; Macrophages; Microbiomes; Monocytes; monocyte‐derived macrophages; Mucosa; neonatal immunity; Neonates; Original; Phagocytosis; Phenotypes; Secretion; Signal transduction; Toll-like receptors; Toll‐like receptor; Tumor necrosis factor-TNF; Tumors; Umbilical cord
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/cei.13108

Summary Bioactive components of human milk, such as human lactoferrin (hLF), play an essential role in gut microbiome homeostasis and protection against neonatal inflammatory diseases. Neonatal intestinal macrophages display a proinflammatory profile that might contribute to inflammatory mucosal injury. Therefore, the aim of the study was to investigate the immunomodulatory effects of hLF on differentiation and activation of monocyte‐derived macrophages (moMϕ). Monocytes isolated from umbilical cord blood of term neonates and peripheral blood of healthy adults were differentiated in the absence or presence of hLF, and differentiation, apoptosis and phagocytosis were evaluated. Cytokine production, Toll‐like receptor (TLR) signalling and activation marker expression were investigated upon activation with lipopolysaccharide (LPS) and lipoteichoic acid (LTA) challenge. We demonstrate that hLF‐differentiated moMϕ exhibit decreased TLR‐4 expression, TLR signalling, proinflammatory cytokine secretion and intracellular tumour necrosis factor (TNF)‐α production. Investigation of differentiation markers, morphology and induction of apoptosis showed no alteration in lactoferrin‐differentiated moMϕ. Taken together, hLF promote anergic/anti‐inflammatory effects by TLR expression and pathway interference, resulting in a diminished proinflammatory moMϕ phenotype. The anergic/anti‐inflammatory properties of hLF might contribute to the prevention of harmful TLR‐mediated inflammatory disorders in the developing gut of premature infants. Neonatal intestinal macrophages display a pro‐inflammatory profile that might contribute to inflammatory mucosal injury. The human bioactive milk component lactoferrin attenuates the pro‐inflammatory immune response of neonatal monocyte‐derived macrophages by interference with TLR‐pathways. Thus, the anergic/anti‐inflammatory properties of human lactoferrin might contribute to the prevention of harmful TLR‐mediated inflammatory disorders in the developing gut of premature infants.