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Published on: May 31, 2018
Bovine Lactoferrin-Induced CCL1 Expression Involves Distinct Receptors in Monocyte-Derived Dendritic Cells and Their
Daniela Latorre1, Nadia Pulvirenti2, Daniela Angela Covino3
1Istituto Superiore di Sanità, Department of Hematology, Oncology and Molecular Medicine, Viale Regina Elena 299, Rome 00161, Italy. daniela.latorre@irb.usi.ch.
Insights
Bovine lactoferrin (bLF) boosts CCL1 chemokine secretion in monocytes and dendritic cells by engaging different receptors. This differential response highlights bLF's complex immunomodulatory role.
Area of Science:
- Immunology
- Cell Biology
Background:
- Lactoferrin (LF) is known for its immunomodulatory properties, including the regulation of cytokine and chemokine secretion.
- Monocytes (Mo) differentiate into dendritic cells (DCs), key players in the immune system.
Purpose of the Study:
- To investigate the effect of bovine lactoferrin (bLF) on CCL1 secretion in monocytes and monocyte-derived dendritic cells (MoDCs).
- To elucidate the specific cell surface receptors involved in bLF-mediated CCL1 modulation.
Main Methods:
- Monocytes and MoDCs were treated with bLF.
- CCL1 secretion and transcript levels were measured.
- Blocking studies using antibodies against CD36 and toll-like receptor (TLR)2 were performed.
Main Results:
- bLF significantly increased CCL1 secretion and transcript accumulation in a concentration- and time-dependent manner in both monocytes and MoDCs.
- CD36 engagement was crucial for bLF-induced CCL1 upregulation in differentiating monocytes.
- TLR2 blocking markedly reduced bLF-induced CCL1 production in MoDCs.
Conclusions:
- bLF differentially modulates CCL1 secretion in monocytes and MoDCs through distinct surface receptors (CD36 and TLR2, respectively).
- These findings underscore the cell-specific immunomodulatory effects of bLF.
- The differential responses may have implications for bLF's role in various physiological and pathological conditions.
Abstract:
Lactoferrin (LF) exhibits a wide range of immunomodulatory activities including modulation of cytokine and chemokine secretion. In this study, we demonstrate that bovine LF (bLF) up-modulates, in a concentration- and time-dependent manner, CCL1 secretion in monocytes (Mo) at the early stage of differentiation toward dendritic cells (DCs), and in fully differentiated immature Mo-derived DCs (MoDCs). In both cell types, up-modulation of CCL1 secretion is an early event following bLF-mediated enhanced accumulation of CCL1 transcripts. Notably, bLF-mediated up-regulation of CCL1 involves the engagement of distinct surface receptors in MoDCs and their Mo precursors. We show that bLF-mediated engagement of CD36 contributes to CCL1 induction in differentiating Mo. Conversely, toll-like receptor (TLR)2 blocking markedly reduces bLF-induced CCL1 production in MoDCs. These findings add further evidence for cell-specific differential responses elicited by bLF through the engagement of distinct TLRs and surface receptors. Furthermore, the different responses observed at early and late stages of Mo differentiation towards DCs may be relevant in mediating bLF effects in specific body districts, where these cell types may be differently represented in physiopathological conditions.
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