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

MBL 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.All 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.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. It has the overall 'bundle-of-tulips' structure first described for C1q [1]. The MBL polypeptide comprises four domains: a cysteine-rich N-terminal domain, a collagen-like region (CLR) that contains Gly-X-Y repeats (where X is any amino acid and Y is often hydroxyproline or hydroxylysine), a neck region and a C-terminal carbohydrate-recognition domain (CRD) [2-7]. The MBL polymer is composed of as many as six homogenous subunits [8], but only the more highly polymeric forms have biological activity and can fix complement.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. To elicit an immune response, DCs must undergo a ma