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

Abstract

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 pro-inflammatory 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) signaling and activation marker expression were investigated upon activation with LPS and LTA challenge. We demonstrate that hLF-differentiated moMϕ exhibit decreased TLR4 expression, TLR signaling, proinflammatory cytokine secretion and intracellular TNFα 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 pro-inflammatory 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. This article is protected by copyright. All rights reserved.