Lactoferrin, a major defense protein of innate immunity, is a novel maturation factor for human dendritic cells

@article{Spadaro2008LactoferrinAM,
  title={Lactoferrin, a major defense protein of innate immunity, is a novel maturation factor for human dendritic cells},
  author={Michela Spadaro and Cristiana Caorsi and Patrizia Ceruti and Atul Varadhachary and Guido Forni and Federica Pericle and Mirella Giovarelli},
  journal={The FASEB Journal},
  year={2008},
  volume={22},
  pages={2747 - 2757}
}
Lactoferrin (LF) is an important protein component of the innate immune system that is broadly distributed within the body fluids. LF is endowed with multiple biological activities. Talactoferrin (TLF), a recombinant human LF, is in clinical development as an anticancer agent and is entering Phase III clinical trials. Here, we show that TLF induces the maturation of human dendritic cells (DCs) derived from monocytes. TLF, at physiologically relevant concentrations (100 µg/ml) up‐regulates the… 
View on Wiley
ncbi.nlm.nih.gov
121 Citations
Highly Influential Citations
5
Background Citations
41
Methods Citations
2
Results Citations
1

121 Citations

Citation Type

Citation Type

Bovine Lactoferrin Counteracts Toll-Like Receptor Mediated Activation Signals in Antigen Presenting Cells
TLDR
It is shown that monocyte-derived dendritic cells generated in the presence of bovine LF fail to undergo activation by up-modulating CD83, co-stimulatory and major histocompatibility complex molecules, and cytokine/chemokine secretion, indicating that bLF exerts a potent anti-inflammatory activity by skewing monocyte differentiation into DCs with impaired capacity to undergoactivation and to promote Th1 responses.
A critical review of the roles of host lactoferrin in immunity
TLDR
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.
Immunomodulatory effects of lactoferrin on antigen presenting cells.
Recombinant human lactoferrin induces human and mouse dendritic cell maturation via Toll‐like receptors 2 and 4
  • M. Spadaro, M. Montone, +6 authors F. Cavallo
  • Biology
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2014
TLDR
Recombinant human lactoferrin induces human and mouse dendritic cell maturation via Toll‐like receptors 2 and 4 and it is shown that TLF triggers the maturation of both human andmouse DCs through TLR‐2 andTLR‐4.
Lactoferrin modulation of BCG-infected dendritic cell functions.
TLDR
A mechanism in which lactoferrin may exert adjuvant activity by enhancing DC function to promote generation of antigen-specific T cells is suggested.
Lactoferrin retargets adenoviruses to TLR4 to induce an abortive NLRP3-associated pyroptotic response in human dendritic cells
TLDR
It is shown that lactoferrin redirects HAdVs from species B, C, and D to toll-like receptor 4 (TLR4) complexes on human mononuclear phagocyte, and TLR4-mediated internalization induces an abortive NLRP3-associated pyroptotic response inducing pro-inflammatory cytokine release and disrupting plasma membrane integrity without cell death.
The human lactoferrin-derived peptide hLF1-11 primes monocytes for an enhanced TLR-mediated immune response
TLDR
Monocytes were primed by hLF1-11 for an enhanced inflammatory response upon TLR4, TLR5, and TLR7 stimulation, but not TLR2 stimulation, which should be taken into account when considering the clinical development of this peptide for a therapeutic intervention in patients.
Lactoferrin Retargets Human Adenoviruses to TLR4 to Induce an Abortive NLRP3-Associated Pyroptotic Response in Human Phagocytes
TLDR
It is shown that lactoferrin redirects HAdV types from species B, C, and D to Toll-like receptor 4 (TLR4) cell surface complexes, which induced an NLRP3-associated response that consisted of cytokine release and transient disruption of plasma membrane integrity, without causing cell death.
Attenuation of massive cytokine response to the staphylococcal enterotoxin B superantigen by the innate immunomodulatory protein lactoferrin
TLDR
It is reported that bovine LF (bLF) was indeed able to attenuate SEB‐induced proliferation, interleukin‐2 production and CD25 expression by human leucocyte antigen (HLA)‐DR4 transgenic mouse T cells and suggest a therapeutic potential for this naturally occurring protein during toxic shock syndrome.
Lactoferrin, a key molecule in immune and inflammatory processes.
  • D. Legrand
  • Biology
    Biochemistry and cell biology = Biochimie et biologie cellulaire
  • 2012
TLDR
Current understanding of the mechanisms that explain the regulatory properties of Lf in immune and inflammatory processes are reviewed.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 70 REFERENCES
Lactoferrin: a modulator of immune and inflammatory responses.
TLDR
Current understanding of the cellular and molecular mechanisms that explain the regulatory properties of lactoferrin in host defence are reviewed.
Lactoferrin activates macrophages via TLR4-dependent and -independent signaling pathways.
Regulation of Dendritic Cell Differentiation by Vasoactive Intestinal Peptide
TLDR
The effect of VIP on the DC‐Treg axis represents an additional mechanism for their general anti‐inflammatory role, particularly relevant in autoimmunity and transplantation.
The Linkage of Innate to Adaptive Immunity via Maturing Dendritic Cells In Vivo Requires CD40 Ligation in Addition to Antigen Presentation and CD80/86 Costimulation
TLDR
The link between innate and adaptive immunity via splenic DCs and innate NKT cells has several components under distinct controls: antigen presentation in the steady state, increases in costimulatory molecules dependent on inflammatory cytokines, and a distinct CD40/CD40L signal that functions together with antigen presentation and costimulation to generate functioning CD4+ T helper cell 1 and CD8+ cytolytic T lymphocytes.
Activated Human γδ T Lymphocytes Express Functional Lactoferrin Receptors
TLDR
The results suggest that Lf is a growth‐supporting factor, especially important in local immune responses in the mucosa, and addition of Lf to cultures containing an optimal concentration of Tr augments the proliferative response to polyclonal T cell activators and alloantigens.
Multifunctional roles of lactoferrin: a critical overview.
TLDR
Recent advances in the understanding of the functions of LF are discussed, including specific interactions with mammalian receptors and microbial components, and the pleoitropic functional nature of this protein.
Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: downregulation by cytokines and bacterial products
TLDR
The capacity of DCs to capture and process antigen could be modulated by exogenous stimuli was investigated and it was found that DCs respond to tumor necrosis factor alpha, CD40 ligand, IL-1, and lipopolysaccharide with a coordinate series of changes that include downregulation of macropinocytosis and Fc receptors, disappearance of the class II compartment, and upregulation of adhesion and costimulatory molecules.
Enhanced Th1 Response to Staphylococcus aureus Infection in Human Lactoferrin-Transgenic Mice1
TLDR
It is demonstrated that human Lf can mediate both antimicrobial and immunomodulatory activities with downstream effects on the outcome of immune pathology in infectious and inflammatory disease.
Differential regulation of chemokine receptors during dendritic cell maturation: a model for their trafficking properties.
TLDR
Concomitantly, the expression of CCR7 and the migration to its ligand EBI1 ligand chemokine (ELC)/macrophage inflammatory protein (MIP)-3beta, a chemokines expressed in lymphoid organs, were strongly up-regulated, though with slower kinetics (24-48 h).
Toll-Like Receptor 4-Dependent Activation of Dendritic Cells by β-Defensin 2
TLDR
It is demonstrated that murine β-defensin 2 (mDF2β) acts directly on immature dendritic cells as an endogenous ligand for Toll-like receptor 4 (TLR-4), inducing up-regulation of costimulatory molecules and d endritic cell maturation, suggesting that mDF2 β may play an important role in immunosurveillance against pathogens and, possibly, self antigens or tumor antigENS.
...
1
2
3
4
5
...