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

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.

Mannose-Binding Lectin Inhibits Monocyte Proliferation through Transforming Growth Factor-β1 and p38 Signaling Pathways

“…Thus, in many ways, our data support an important role for MBL in the regulation of adaptive immunity and inflammatory responses. Additionally, higher concentrations of MBL could inhibit LPS-induced DC maturation, and the secretion of pro-inflammatory cytokines like TNF-α and IL-12, and reduce the ability of antigen presenting cells (APCs) to stimulate allogeneic T lymphocyte proliferation [11]. These observations indicate that MBL could be implicated in both the anti-inflammatory effect and immunoregulation.…”

“…MBL has been reported to regulate dendritic cell (DC) maturation, and cytokine production on activation by bacterial lipopolysaccharide (LPS) [11], and may influence the cytokine network after stimulation by various microorganisms [12]. Stimulation of mature DCs by culturing them in the presence of recombinant human MBL (rhMBL) and subsequently co-culturing the MBL-exposed DCs with allogeneic mononuclear cells, markedly promoted the secretion of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in vitro [13].…”

Immunoproteasomes Shape the Transcriptome and Regulate the Function of Dendritic Cells

“…We found that nine of the top DEGs between WT and dKO DCs ($10-fold difference) were involved in DC function (Table I) (36)(37)(38)(39)(40)(41)(42)(43)(44). Genes expressed at low levels (#0.1 reads/kb/million mapped reads) were excluded from this analysis.…”

Differences in MBL levels between juvenile patients newly diagnosed with type 1 diabetes and their healthy siblings

“…Both high and low levels of MBL could be involved in the pathogeneses of autoimmune diseases (Bouwman et al, 2006). High levels of MBL, might result in excessive component activation and prime adaptive immune response, but on the other hand suppress cytokine release (Jack et al, 2001;Wang et al, 2011). Low levels of MBL might enhance adaptive autoimmune response, because of impaired clearance of apoptotic and necrotic cells (Bouwman et al, 2006;Nauta et al, 2003) and enhanced cytokine release (Jack et al, 2001).…”

“…There is evidence that MBL function includes activation of the complement system through the lectin pathway in association with MBL-associated serine proteases (MASPs) (Degn and Thiel, 2013), affecting inflammation by complex modulation of cytokine release (Jack et al, 2001;Wang et al, 2011), facilitating phagocytosis of apoptotic cells by macrophages (Nauta et al, 2003)-and might have a not yet clear role in opsonosphagocytosis (Neth et al, 2002 MBL has also been proposed as an acute phase response protein in relation to infection, but this response seems to be highly dependent on genotype (Herpers et al, 2009).…”