DC-SIGN Mediates Binding of Dendritic Cells to Authentic Pseudo-LewisY Glycolipids of Schistosoma mansoni Cercariae, the First Parasite-specific Ligand of DC-SIGN

Meyer, Sandra De; Liempt, Ellis van; Imberty, Anne; Kooyk, Yvette van; Geyer, Hildegard; Geyer, Rudolf; Die, Irma van

doi:10.1074/jbc.m507100200

Cited by 88 publications

(73 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For instance, SEA, which contains glycoproteins, is recognized and internalized by human DC in a DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN)-, mannose receptor-and macrophage galactose-type lectin-dependent manner [16,17]. Antigen preparations of other stages of the schistosome life cycle have also been shown to interact with DC-SIGN [18]. Binding of SEA to DC-SIGN is dependent on the sugar motifs Le x and LDN-F [17], while chemical modification of the glycans present in SEA abolishes the Th2-driving capacity of SEA [19].…”

Section: Modulation Of DC Function By Direct Interaction With Helmintmentioning

confidence: 99%

Helminths and dendritic cells: Sensing and regulating via pattern recognition receptors, Th2 and Treg responses

et al. 2010

View full text Add to dashboard Cite

The classical reaction of the host to helminth infections is the induction of Th2 immune responses with a regulatory component. DC, as central players in the induction and maintenance of immune responses, play a prominent role in both these processes, and in recent years considerable progress has been made in elucidating the mechanisms behind the interplay between DC and helminths. It is becoming increasingly clear that helminths modulate DC function not only via direct interactions but also indirectly via host-derived cues. Furthermore, while studies have until recently focused on receptor signalingmediated DC modulation by helminths, evidence is emerging that DC may also respond to helminth infections by sensing stress signals or tissue damage inflicted by the worms or their products. Here, we will discuss these new insights and will link them to the origin and importance of Th2 and regulatory immune responses with respect to the survival of both parasite and host.Key words: DC . Helminth . Th cell polarization . Tissue damage IntroductionThe classical reaction of the host to helminth infections is the induction of Th2 responses. The induction of Th2 immunity has been shown to be important for resistance to helminth infections in various model systems; however, despite induction of a Th2 response, total clearance of the parasites rarely occurs in man (reviewed in [1,2]). This implies that helminths have evolved strategies, such as evasion or suppression of the host immune response that prevent their expulsion and permit their long-term survival. The immune modulatory effects are thought to arise from the helminth's capacity to exploit the host's own system of immune regulation, which is normally crucial for the maintenance of immune homeostasis and self tolerance. In this respect, the induction of Treg has been shown to be one of the most common mechanisms that restrains immune responses against the parasite while also preventing excessive inflammation and tissue damage inflicted by the worms (reviewed in [2,3]). Therefore, it is not surprising that among the variety of mechanisms developed by helminths to influence host immune responses, modulation of DC as pivotal players in the initiation and polarization of adaptive immune responses, including Treg modulation, may have a particularly important role (reviewed in [2,4,5] ) carbohydrate epitope found in schistosoma soluble egg antigens (SEA), has been implicated in TLR4-dependent priming of Th2 responses via DC [9]. However, SEA is also known to be capable of modulating DC for Th2 priming in the absence of TLR signaling [10]. Furthermore, phosphatidylserine (PS) lipids derived from schistosomes and ascaris worms, which carry TLR2-activating molecules, have been shown to promote Th2 responses via DC, but this is not TLR2 dependent [11], whereas monoacetylated PS lipids from schistosomes were found to specifically instruct DC to preferentially induce IL-10-producing Treg in a TLR2-dependent fashion [12]. Although TLR2 does not seem to be essential for Th2 polar...

show abstract

Section: Modulation Of DC Function By Direct Interaction With Helmintmentioning

confidence: 99%

Helminths and dendritic cells: Sensing and regulating via pattern recognition receptors, Th2 and Treg responses

et al. 2010

View full text Add to dashboard Cite

show abstract

“…One of the best studied CLRs is the DC-specific ICAM-3-grabbing nonintegrin, also known as DC-SIGN (8). Besides a pattern recognition receptor for HIV-1 (9), CMV (10), Schistosoma mansoni (11), and other pathogens (5,12), DC-SIGN has been shown to also recognize glycan epitopes on endogenous ligands, such as ICAM-2 on endothelial cells (6), ICAM-3 on T cells (8), or Mac1 on neutrophils (13). Interaction of DC-SIGN with its ligands regulates DC precursor migration into peripheral tissues, stabilizes the DC-T cell contact surface in the immunological synapse (14), and allows neutrophils to induce DC maturation, respectively.…”

Section: Endritic Cells (Dc)mentioning

confidence: 99%

Dendritic Cell Maturation Results in Pronounced Changes in Glycan Expression Affecting Recognition by Siglecs and Galectins

Bax

García-Vallejo

Jang-Lee

et al. 2007

The Journal of Immunology

Self Cite

110

View full text Add to dashboard Cite

“…Interestingly, the structures of IF-S and the A. fumigatus galactomannan differ from those of the LewisX [Gal␤1-4(Fuc␣1-3)GlcNAc] and pseudo-LewisY [Fuc␣1-3Gal␤1-4(Fuc␣1-3)GlcNAc] determinants, which are the DC-SIGN glycolipid ligands in Schistosoma mansoni cercariae (29). The flexibility in the sugar recognition activity of DC-SIGN is thought to be the basis for its ability to recognize a large array of pathogens, all of which target DC-SIGN probably as a means of evading the immune response (47).…”

Section: Discussionmentioning

confidence: 99%

AM3 Modulates Dendritic Cell Pathogen Recognition Capabilities by Targeting DC-SIGN

Serrano‐Gómez

Martínez-Nuñez

Sierra‐Filardi

et al. 2007

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Inmunoferon is an immunomodulatory drug whose active principle (AM3) is a glycoconjugate of natural origin composed of a glucomannan polysaccharide from Candida utilis and a storage protein from nongerminated seeds of Ricinus communis (49). In vivo, AM3 enhances lymphocyte proliferation, interleukin-2 (IL-2) production, and NK activity (37); functions as an adjuvant to hepatitis B revaccination in nonresponder healthy persons (32, 38); and partially rescues the defective natural killer and phagocytic activities seen in chronic obstructive pulmonary disease patients (34). Besides, oral administration of AM3 increases IL-10 and reduces lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-␣), IL-1␤, and inducible nitric oxide synthase; and thus, AM3 acts as a modulator of the innate immune system by acting on peripheral blood mononuclear cells (5, 25).Dendritic cells (DCs) are professional antigen-presenting cells which link the innate and adaptive branches of the immune response by virtue of their capacity to recognize pathogen-associated structures and promote the initiation of Tcell-dependent immunity (3). In the steady state, immature myeloid DCs display a potent antigen uptake ability and contribute to the establishment of peripheral tolerance (41), whereas mature DCs display a strong capacity for T-cell stimulation and polarization of the immune response. Pathogen recognition by immature DCs is carried out by a number of cell surface molecules named pathogen-associated molecular pattern receptors, which include the Toll-like receptor (TLR) family (44) and a large number of lectins and lectin-like molecules (48), including the DC-specific intercellular adhesion molecule 3 (ICAM-3)-grabbing nonintegrin (DC-SIGN; CD209) lectin. DC-SIGN is a type II membrane C-type lectin (13,16,21) which recognizes a large array of viral, bacterial, fungal, and parasite pathogens (1, 7, 9, 12, 22-24, 33, 40, 43, 45) in a mannan-and a Lewis oligosaccharide-dependent manner (17, 18) and which mediates DC interactions with naïve T lymphocytes, endothelial cells, and neutrophils by recognition of ICAM-3 (21), ICAM-2 (19), and Mac-1 (46), respectively.Given its adjuvant and immunomodulatory effects, we have hypothesized that AM3 might have a direct effect on DCs. In fact, AM3 triggers DC maturation and promotes the preferential release of IL-10 from mature human monocyte-derived DCs (P. Majano et al., submitted for publication). Since fungus-derived mannans are capable of inhibiting the lymphoproliferative responses of human mononuclear leukocytes (4, 40) and modulate pathogen recognition by human DCs (40), the effects of the polysaccharide moiety of AM3 (IF-S) on the effector functions of immature human monocyte-derived DCs were analyzed. In the present report we present evidence that the polysaccharide moiety of AM3 directly influences pathogen

show abstract

DC-SIGN Mediates Binding of Dendritic Cells to Authentic Pseudo-LewisY Glycolipids of Schistosoma mansoni Cercariae, the First Parasite-specific Ligand of DC-SIGN

Cited by 88 publications

References 55 publications

Helminths and dendritic cells: Sensing and regulating via pattern recognition receptors, Th2 and Treg responses

Helminths and dendritic cells: Sensing and regulating via pattern recognition receptors, Th2 and Treg responses

Dendritic Cell Maturation Results in Pronounced Changes in Glycan Expression Affecting Recognition by Siglecs and Galectins

AM3 Modulates Dendritic Cell Pathogen Recognition Capabilities by Targeting DC-SIGN

Contact Info

Product

Resources

About