The serum mannose-binding protein and the macrophage mannose receptor are pattern recognition molecules that link innate and adaptive immunity

Ip, Fraser; Koziel, Henryk; Ra, Ezekowitz

doi:10.1006/smim.1998.0141

Cited by 199 publications

(126 citation statements)

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“…Mannose receptors contain multiple C-type lectin-like domains each capable of binding specific monosaccharides such as mannose, fucose, and N-acetylglucosamine. Although endocytosis requires signaling through a conserved tyrosine-based FENTLY motif in the cytoplasmic tail of the receptor (East and Isacke, 2002), the signaling molecules mediating phagocytosis and the downstream cell signaling pathways remain undefined (Fraser et al, 1998). The current study demonstrates that mannose receptor-mediated phagocytosis was associated with focal F-actin polymerization, dependent on Cdc42 and Rho activation, and dependent on the Rho effector molecule, Rock.…”

Section: Discussionmentioning

confidence: 68%

Cdc42 and RhoB Activation Are Required for Mannose Receptor-mediated Phagocytosis by Human Alveolar Macrophages

Zhang

Zhu

et al. 2005

MBoC

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Human alveolar macrophages (AMs) phagocytose Pneumocystis (Pc) organisms predominantly through mannose receptors, although the molecular mechanism mediating this opsonin-independent process is not known. In this study, using AMs from healthy individuals, Pc phagocytosis was associated with focal F-actin polymerization and Cdc42, Rac1, and Rho activation in a time-dependent manner. Phagocytosis was primarily dependent on Cdc42 and RhoB activation (as determined by AM transfection with Cdc42 and RhoB dominant-negative alleles) and mediated predominantly through mannose receptors (as determined by siRNA gene silencing of AM mannose receptors). Pc also promoted PAK-1 phosphorylation, which was also dependent on RhoGTPase activation. HIV infection of AMs (as a model for reduced mannose receptor expression and function) was associated with impaired F-actin polymerization, reduced Cdc42 and Rho activation, and markedly reduced PAK-1 phosphorylation in response to Pc organisms. In healthy AMs, Pc phagocytosis was partially dependent on PAK activation, but dependent on the Rho effector molecule ROCK. These data provide a molecular mechanism for AM mannose receptor-mediated phagocytosis of unopsonized Pc organisms that appears distinct from opsonin-dependent phagocytic receptors. Reduced AM mannose receptor-mediated Cdc42 and Rho activation in the context of HIV infection may represent a mechanism that contributes to the pathogenesis of opportunistic pneumonia.

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Section: Discussionmentioning

confidence: 68%

Cdc42 and RhoB Activation Are Required for Mannose Receptor-mediated Phagocytosis by Human Alveolar Macrophages

Zhang

Zhu

et al. 2005

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“…Only expression of DC-SIGN, however, is restricted to DCs. The MR has multiple CRDs and has been demonstrated to internalize a variety of glycoproteins from microorganisms by macrophages (38). Therefore, mannose-binding receptors may play an important role in the initiation of immune responses against a diversity of microorganisms.…”

Section: C-type Lectins As Ag Receptors On Dcsmentioning

confidence: 99%

The Dendritic Cell-Specific Adhesion Receptor DC-SIGN Internalizes Antigen for Presentation to T Cells

Engering¹,

Geijtenbeek²,

Vliet³

et al. 2002

The Journal of Immunology

568

500

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Dendritic cells (DCs) capture Ags or viruses in peripheral tissue to transport them to lymphoid organs to induce cellular T cell responses. Recently, a DC-specific C-type lectin was identified, DC-specific ICAM-grabbing non-integrin (DC-SIGN), that functions as cell adhesion receptor mediating both DC migration and T cell activation. DC-SIGN also functions as an HIV-1R that captures HIVgp120 and facilitates DC-induced HIV transmission of T cells. Internalization motifs in the cytoplasmic tail of DC-SIGN hint to a function of DC-SIGN as endocytic receptor. In this study we demonstrate that on DCs DC-SIGN is rapidly internalized upon binding of soluble ligand. Mutating a putative internalization motif in the cytoplasmic tail reduces ligand-induced internalization. Detailed analysis using ratio fluorescence imaging and electron microscopy showed that DC-SIGN-ligand complexes are targeted to late endosomes/lysosomes. Moreover, ligands internalized by DC-SIGN are efficiently processed and presented to CD4+ T cells. The distinct pattern of expression of C-type lectins on DCs in situ and their nonoverlapping Ag recognition profile hint to selective functions of these receptors to allow a DC to recognize a wide variety of Ags and to process these to induce T cell activation. These data point to a novel function of the adhesion receptor DC-SIGN as an efficient DC-specific Ag receptor that can be used as a target to induce viral and antitumor immunity.

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“…When binding to the collectin receptor of effector cells, MBL can mediate direct opsonization and MBL-dependent, cell-mediated cytotoxicity. 12 MBL also plays an important role in defense in surface mucous membranes. 13 As such, MBL has been considered to be a key molecule in the regulation of innate immunity.…”

Section: Mannan-binding Lectin (Mbl) a Camentioning

confidence: 99%

Mannan-binding lectin directly interacts with Toll-like receptor 4 and suppresses lipopolysaccharide-induced inflammatory cytokine secretion from THP-1 cells

et al. 2011

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Mannan-binding lectin (MBL) plays a key role in the lectin pathway of complement activation and can influence cytokine expression. Toll-like receptor 4 (TLR4) is expressed extensively and has been demonstrated to be involved in lipopolysaccharide (LPS)-induced signaling. We first sought to determine whether MBL exposure could modulate LPS-induced inflammatory cytokine secretion and nuclear factor-kB (NF-kB) activity by using the monocytoid cell line THP-1. We then investigated the possible mechanisms underlying any observed regulatory effect. Using ELISA and reverse transcriptase polymerase chain reaction (RT-PCR) analysis, we found that at both the protein and mRNA levels, treatment with MBL suppresses LPS-induced tumor-necrosis factor (TNF)-a and IL-12 production in THP-1 cells. An electrophoretic mobility shift assay and western blot analysis revealed that MBL treatment can inhibit LPS-induced NF-kB DNA binding and translocation in THP-1 cells. While the binding of MBL to THP-1 cells was evident at physiological calcium concentrations, this binding occurred optimally in response to supraphysiological calcium concentrations. This binding can be partly inhibited by treatment with either a soluble form of recombinant TLR4 extracellular domain or anti-TLR4 monoclonal antibody (HTA125). Activation of THP-1 cells by LPS treatment resulted in increased MBL binding. We also observed that MBL could directly bind to the extracellular domain of TLR4 in a dose-dependent manner, and this interaction could attenuate the binding of LPS to cell surfaces. Taken together, these data suggest that MBL may affect cytokine expression through modulation of LPS-/TLR-signaling pathways. These findings suggest that MBL may play an important role in both immune regulation and the signaling pathways involved in cytokine networks.

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The serum mannose-binding protein and the macrophage mannose receptor are pattern recognition molecules that link innate and adaptive immunity

Cited by 199 publications

References 0 publications

Cdc42 and RhoB Activation Are Required for Mannose Receptor-mediated Phagocytosis by Human Alveolar Macrophages

Cdc42 and RhoB Activation Are Required for Mannose Receptor-mediated Phagocytosis by Human Alveolar Macrophages

The Dendritic Cell-Specific Adhesion Receptor DC-SIGN Internalizes Antigen for Presentation to T Cells

Mannan-binding lectin directly interacts with Toll-like receptor 4 and suppresses lipopolysaccharide-induced inflammatory cytokine secretion from THP-1 cells

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