Mannan-binding lectin regulates dendritic cell maturation and cytokine production induced by lipopolysaccharide

Mingyong Wang,Yue Chen,Yani Zhang,Zhengliang Chen,Xiao Lu,Liyun Zhang

doi:10.1186/1471-2172-12-1

Abstract

BackgroundMannan-binding lectin (MBL) is a pattern-recognition molecule present in serum, which is involved in the innate immune defense by activating complement and promoting opsonophagocytosis. Dendritic cells (DCs) are professional antigen presenting cells (APCs) that are crucial for the initiation of adaptive immunity. Lipopolysaccharide (LPS) has been shown to be a strong activator of the inflammatory response and immune regulation. We first examined whether MBL modulated LPS-induced cellular responses, then investigated possible mechanisms of its inhibitory effect.ResultsMBL at higher concentrations (10-20 μg/ml) significantly attenuated LPS-induced maturation of monocyte-derived DCs (MDCs) and production of proinflammatory cytokines (e.g., IL-12 and TNF-α), and inhibited their ability to activate allogeneic T lymphocytes. It bound to immature MDCs at physiological calcium concentrations, and was optimal at supraphysiological calcium concentrations. MBL also bound directly to immature MDCs and attenuated the binding of LPS to the cell surfaces, resulting in decreased LPS-induced nuclear factor-κB (NF-κB) activity in these cells.ConclusionAll these data suggest that MBL could affect the functions of DCs by modifying LPS-induced cellular responses. This study supports an important role for MBL in the regulation of adaptive immune responses and inflammatory responses.

Highlights

Mannan-binding lectin (MBL) is a pattern-recognition molecule present in serum, which is involved in the innate immune defense by activating complement and promoting opsonophagocytosis
MBL suppresses LPS-induced monocyte-derived dendritic cell (MDC) maturation It is well known that dendritic cell (DC) maturation is induced by LPS
Inclusion of anti-MBL polyclonal antibody during the preincubation of the cells with MBL restored the expression of CD83, CD86, and MHC II on DCs (Figure 2), indicating that MBL inhibited the interaction between LPS and imMDCs

Summary

Introduction

Mannan-binding lectin (MBL) is a pattern-recognition molecule present in serum, which is involved in the innate immune defense by activating complement and promoting opsonophagocytosis. Mannan-binding lectin (MBL), a member of the collectin family in the C-type lectin superfamily, is a multimeric protein containing collagen-like sequences. It is synthesized and secreted into the blood by hepatocytes. Dendritic cells (DCs) are highly efficient antigen-presenting cells that play a central role in orchestrating adaptive immune responses to pathogens [9]. In their immature form (imDCs), they can capture antigen very efficiently by macropinocytosis, endocytosis [10], and phagocytosis [11] through different cell surface molecules, e.g. mannose receptor, Toll-like receptors (TLRs) or scavenger receptors. DC maturation is known to be induced by several stimuli, including bacterial components [e.g., lipopolysaccharide (LPS)], heat shock proteins, viral products (e.g., dsRNA) and endogenous factors such as inflammatory cytokines [12]

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Results

Conclusion