A critical review of the roles of host lactoferrin in immunity

Abstract

Lactoferrin (Lf) is an essential element of innate immunity, which refers to antigen-nonspecific defense mechanisms that a host uses immediately or within hours after exposure to an antigen. Following infection, Lf is released from neutrophils (PMNs) in blood and inflamed tissues and, such as other soluble pattern-recognition receptors of the innate immunity, Lf recognizes unique microbial molecules called pathogen-associated molecular patterns (PAMPs): LPS from the gram-negative cell wall and bacterial unmethylated CpG DNA. However, unlike classical PAMPs receptors involved in the activation of immune cells, Lf may act either as a competitor for these receptors or as a partner molecule, depending on the physiological status of the organism. These immunomodulatory properties are explained by the ability of Lf to interact with proteoglycans and receptors on the surface of mammalian cells: cells of the innate (NK cells, neutrophils, macrophages, basophils, neutrophils and mast cells) and adaptive [lymphocytes and antigen-presenting cells (APCs)] immune systems, and also epithelial and endothelial cells. Through these interactions, Lf is able to modulate the migration, maturation and functions of immune cells, and thus to influence both adaptive and innate immunities. The understanding of the roles of the host-expressed Lf in immunity comes from in vivo and in vitro studies with exogenous Lf which, although informative, rarely reflect the pathological, or non-pathological, conditions in the organism. In this review, the data from the literature will be critically analyzed in order to present a real picture of the regulatory roles of host Lf in immunity.

Inhibition of initial bacterial adhesion on titanium surfaces by lactoferrin coating

“…[13][14][15] LF has bacteriostatic and bactericidal activities and is involved in host immune defense. 13,16,17 There are some reports that LF can inhibit the adhesion of oral bacteria and Candida albicans on hydroxyapatite, 18,19 dental polymers, 20 and glass disks. 21 However, there are no reports about the effect of a LF coating on dental abutment materials.…”

Lactoferrin suppresses the Epstein–Barr virus-induced inflammatory response by interfering with pattern recognition of TLR2 and TLR9

“…Multiple biological functions have been described for LF, including iron homeostasis, antiinflammatory activity, immunomodulation, cancer protection, and antimicrobial activity. [13][14][15] Although the cellular and molecular mechanisms accounting for the immunemodulatory effects of LF are far from being fully elucidated, it is now clear that the capacity of LF to influence cytokine production, either negatively or positively, relies, at least in part, on its ability to bind and sequester both lipopolysaccharide and its receptor CD14, as well as CpG DNA, thus preventing the downstream activation of pro-inflammatory pathways. [16][17][18] Through the linkage analysis of 18 pedigrees from the Hunan province of South China, we previously revealed that potential susceptibility loci related to NPC are located on chromosome 3p21.…”

Structural Basis for Hemoglobin Capture by Staphylococcus aureus Cell-surface Protein, IsdH

“…Most iron is sequestered within cells, and serum iron is kept at an extremely low concentration (ϳ10 Ϫ24 M) by the iron transport protein transferrin (2). A related protein, lactoferrin, is present in exocrine solutions such as tears and milk and is also released from neutrophils at sites of infection (3). Iron uptake and homeostasis are even tuned toward anemia in chronic infection by the hormone hepcidin (4).…”