Dendritic cells and C‐type lectin receptors: coupling innate to adaptive immune responses

Dendritic cells (DCs) have an important function in the initiation and differentiation of immune responses, linking innate information to tailored adaptive responses. Depending on the pathogen invading the body, specific immune responses are built up that are crucial for eliminating the pathogen from the host. Host recognition of invading microorganisms relies on evolutionarily ancient, germline‐encoded pattern recognition receptors (PRRs) that are highly expressed on the cell surface of DCs, of which the Toll‐like receptors (TLRs) are well characterized and recognize bacterial or viral components. Moreover, they bind a variety of self‐proteins released from damaged tissues including several heat‐shock proteins. The membrane‐associated C‐type lectin receptors (CLRs) recognize glycan structures expressed by host cells of the immune system or on specific tissues, which upon recognition allow cellular interactions between DCs and other immune or tissue cells. In addition, CLRs can function as PRRs. In contrast to TLRs, CLRs recognize carbohydrate structures present on the pathogens. Modification of glycan structures on pathogens to mimic host glycans can thereby alter CLR interactions that subsequently modifies DC‐induced polarization. In this review, we will discuss in detail how specific glycosylation of antigens can dictate both the innate and adaptive interactions that are mediated by CLRs on DCs and how this balances immune activation and inhibition of DC function.

[1]  C. Janeway,et al.  Innate immune recognition. , 2002, Annual review of immunology.

[2]  A. Prescott,et al.  Enhanced Dendritic Cell Antigen Capture via Toll-Like Receptor-Induced Actin Remodeling , 2004, Science.

[3]  A. Azad,et al.  The human macrophage mannose receptor directs Mycobacterium tuberculosis lipoarabinomannan-mediated phagosome biogenesis , 2005, The Journal of experimental medicine.

[4]  M. Netea,et al.  Syk kinase is required for collaborative cytokine production induced through Dectin-1 and Toll-like receptors , 2008, European journal of immunology.

[5]  C. Sousa Faculty Opinions recommendation of Dectin-1 mediates the biological effects of beta-glucans. , 2003 .

[6]  T. van der Poll,et al.  Salp15 Binding to DC-SIGN Inhibits Cytokine Expression by Impairing both Nucleosome Remodeling and mRNA Stabilization , 2008, PLoS pathogens.

[7]  Christine A. Wells,et al.  The Macrophage-Inducible C-Type Lectin, Mincle, Is an Essential Component of the Innate Immune Response to Candida albicans1 , 2008, The Journal of Immunology.

[8]  S. Gordon,et al.  Syk-dependent cytokine induction by Dectin-1 reveals a novel pattern recognition pathway for C type lectins. , 2005, Immunity.

[9]  Y. Kooyk,et al.  C-Type Lectin DC-SIGN Modulates Toll-like Receptor Signaling via Raf-1 Kinase-Dependent Acetylation of Transcription Factor NF-κB , 2007 .

[10]  A. Lanzavecchia,et al.  The mannose receptor functions as a high capacity and broad specificity antigen receptor in human dendritic cells , 1997, European journal of immunology.

[11]  R. Callard,et al.  Neisseria meningitidis expressing lgtB lipopolysaccharide targets DC‐SIGN and modulates dendritic cell function , 2006, Cellular microbiology.

[12]  D. Kasper,et al.  A bacterial carbohydrate links innate and adaptive responses through Toll-like receptor 2 , 2006, The Journal of experimental medicine.

[13]  C. Figdor,et al.  Targeting DCIR on human plasmacytoid dendritic cells results in antigen presentation and inhibits IFN-alpha production. , 2008, Blood.

[14]  Gordon D. Brown Dectin-1: a signalling non-TLR pattern-recognition receptor , 2006, Nature Reviews Immunology.

[15]  S. Gordon,et al.  Identification and Characterization of a Novel Human Myeloid Inhibitory C-type Lectin-like Receptor (MICL) That Is Predominantly Expressed on Granulocytes and Monocytes* , 2004, Journal of Biological Chemistry.

[16]  A. V. van Bodegraven,et al.  Helicobacter pylori Modulates the T Helper Cell 1/T Helper Cell 2 Balance through Phase-variable Interaction between Lipopolysaccharide and DC-SIGN , 2004, The Journal of experimental medicine.

[17]  G. Vriend,et al.  Identification of Different Binding Sites in the Dendritic Cell-specific Receptor DC-SIGN for Intercellular Adhesion Molecule 3 and HIV-1* , 2002, The Journal of Biological Chemistry.

[18]  F. Hanisch,et al.  Human Tumor Antigen MUC1 Is Chemotactic for Immature Dendritic Cells and Elicits Maturation but Does Not Promote Th1 Type Immunity 1 , 2005, The Journal of Immunology.

[19]  M. Deckert,et al.  The immunological synapse and Rho GTPases. , 2005, Current topics in microbiology and immunology.

[20]  S. Gordon,et al.  Dectin-1 Mediates the Biological Effects of β-Glucans , 2003, The Journal of experimental medicine.

[21]  Sara Alonso,et al.  Costimulation of Dectin-1 and DC-SIGN Triggers the Arachidonic Acid Cascade in Human Monocyte-Derived Dendritic Cells1 , 2008, The Journal of Immunology.

[22]  T. Geijtenbeek,et al.  Mycobacteria Target DC-SIGN to Suppress Dendritic Cell Function , 2003, The Journal of experimental medicine.

[23]  J. Trowsdale,et al.  The B7 Homolog Butyrophilin BTN2A1 Is a Novel Ligand for DC-SIGN1 , 2007, The Journal of Immunology.

[24]  G. Nabel,et al.  Leukocyte-specific protein 1 interacts with DC-SIGN and mediates transport of HIV to the proteasome in dendritic cells , 2007, The Journal of experimental medicine.

[25]  G. Meijer,et al.  The C-type lectin MGL expressed by dendritic cells detects glycan changes on MUC1 in colon carcinoma , 2007, Cancer Immunology, Immunotherapy.

[26]  A. Enk,et al.  Induction of CD4+/CD25+ regulatory T cells by targeting of antigens to immature dendritic cells. , 2003, Blood.

[27]  Richard D Cummings,et al.  The dendritic cell-specific C-type lectin DC-SIGN is a receptor for Schistosoma mansoni egg antigens and recognizes the glycan antigen Lewis x. , 2003, Glycobiology.

[28]  J. Belisle,et al.  Langerhans cells utilize CD1a and langerin to efficiently present nonpeptide antigens to T cells. , 2004, The Journal of clinical investigation.

[29]  I. Brockhausen Pathways of O-glycan biosynthesis in cancer cells. , 1999, Biochimica et biophysica acta.

[30]  S. Gringhuis,et al.  DC-SIGN mediates adhesion and rolling of dendritic cells on primary human umbilical vein endothelial cells through LewisY antigen expressed on ICAM-2. , 2008, Molecular immunology.

[31]  M. Wiznerowicz,et al.  Lentivirus-mediated Rna Interference of Dc-sign Expression Inhibits Human Immunodeficiency Virus Transmission from Dendritic Cells to T Cells in the Early Events of Human Immunodeficiency Virus Type 1 (hiv-1) Infection, Immature Dendritic Cells (dcs) Expressing the Dc-specific Intercellular Adhesion , 2022 .

[32]  S. Gordon,et al.  Dectin-1 is required for beta-glucan recognition and control of fungal infection. , 2007, Nature immunology.

[33]  T. Geijtenbeek,et al.  Cutting Edge: Carbohydrate Profiling Identifies New Pathogens That Interact with Dendritic Cell-Specific ICAM-3-Grabbing Nonintegrin on Dendritic Cells , 2003, The Journal of Immunology.

[34]  T. Okazaki,et al.  DCIR acts as an inhibitory receptor depending on its immunoreceptor tyrosine-based inhibitory motif. , 2002, The Journal of investigative dermatology.

[35]  Y. Kooyk,et al.  Langerin is a natural barrier to HIV-1 transmission by Langerhans cells , 2007, Nature Medicine.

[36]  Antonio Lanzavecchia,et al.  The Dendritic Cell-Specific Adhesion Receptor DC-SIGN Internalizes Antigen for Presentation to T Cells1 , 2002, The Journal of Immunology.

[37]  Maureen E. Taylor,et al.  Introduction to glycobiology , 2003 .

[38]  G. Meijer,et al.  Dendritic cells recognize tumor-specific glycosylation of carcinoembryonic antigen on colorectal cancer cells through dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin. , 2005, Cancer research.

[39]  J. Gready,et al.  The C‐type lectin‐like domain superfamily , 2005, The FEBS journal.

[40]  Y. Kawaoka,et al.  Human Macrophage C-Type Lectin Specific for Galactose and N-Acetylgalactosamine Promotes Filovirus Entry , 2004, Journal of Virology.

[41]  S. Gordon,et al.  The mannose receptor: linking homeostasis and immunity through sugar recognition. , 2005, Trends in immunology.

[42]  D. Underhill,et al.  Dectin‐1 mediates macrophage recognition of Candida albicans yeast but not filaments , 2005, The EMBO journal.

[43]  J. Rodríguez-Fernández,et al.  DC-SIGN ligation on dendritic cells results in ERK and PI3K activation and modulates cytokine production. , 2006, Blood.

[44]  Sejal Patel,et al.  APCs express DCIR, a novel C-type lectin surface receptor containing an immunoreceptor tyrosine-based inhibitory motif. , 1999, Journal of immunology.

[45]  R. Coffman,et al.  Toll-like receptor recognition regulates immunodominance in an antimicrobial CD4+ T cell response. , 2006, Immunity.

[46]  R. Medzhitov,et al.  Toll-dependent selection of microbial antigens for presentation by dendritic cells , 2006, Nature.

[47]  M. Tremblay,et al.  The C-type lectin surface receptor DCIR acts as a new attachment factor for HIV-1 in dendritic cells and contributes to trans- and cis-infection pathways. , 2008, Blood.

[48]  S. Gringhuis,et al.  C-type lectin DC-SIGN modulates Toll-like receptor signaling via Raf-1 kinase-dependent acetylation of transcription factor NF-kappaB. , 2007, Immunity.

[49]  S. Depraetere,et al.  Hepatitis C Virus Targets DC-SIGN and L-SIGN To Escape Lysosomal Degradation , 2004, Journal of Virology.

[50]  R. Steinman,et al.  DC-SIGN ( CD 209 ) Mediates Dengue Virus Infection of Human Dendritic Cells , 2003 .

[51]  R. Steinman,et al.  DC-SIGN (CD209) Mediates Dengue Virus Infection of Human Dendritic Cells , 2003, The Journal of experimental medicine.

[52]  Y. Kooyk,et al.  Regulation of effector T cells by antigen-presenting cells via interaction of the C-type lectin MGL with CD45 , 2006, Nature Immunology.

[53]  T. Feizi,et al.  New structural insights into lectin-type proteins of the immune system. , 2001, Current opinion in structural biology.

[54]  R. Tampé,et al.  Spatial and mechanistic separation of cross-presentation and endogenous antigen presentation , 2008, Nature Immunology.

[55]  L. O’Neill,et al.  TLRs, NLRs and RLRs: a trinity of pathogen sensors that co-operate in innate immunity. , 2006, Trends in immunology.

[56]  S. Diebold Innate recognition of viruses. , 2010, Immunology letters.

[57]  R. Steinman,et al.  The Dendritic Cell Receptor for Endocytosis, Dec-205, Can Recycle and Enhance Antigen Presentation via Major Histocompatibility Complex Class II–Positive Lysosomal Compartments , 2000, The Journal of cell biology.

[58]  Sven Burgdorf,et al.  Distinct Pathways of Antigen Uptake and Intracellular Routing in CD4 and CD8 T Cell Activation , 2007, Science.

[59]  J. Ruland,et al.  Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17 , 2007, Nature Immunology.

[60]  Ola Blixt,et al.  Carbohydrate profiling reveals a distinctive role for the C-type lectin MGL in the recognition of helminth parasites and tumor antigens by dendritic cells. , 2005, International immunology.

[61]  M. Wright,et al.  Dectin-1 Interaction with Tetraspanin CD37 Inhibits IL-6 Production1 , 2007, The Journal of Immunology.

[62]  A. Pichlmair,et al.  Innate recognition of viruses. , 2007, Immunity.

[63]  W. Weis,et al.  The C‐type lectin superfamily in the immune system , 1998, Immunological reviews.

[64]  D. Underhill,et al.  Dectin-1 activates Syk tyrosine kinase in a dynamic subset of macrophages for reactive oxygen production. , 2005, Blood.

[65]  T. Irimura,et al.  Tumor-associated Tn-MUC1 glycoform is internalized through the macrophage galactose-type C-type lectin and delivered to the HLA class I and II compartments in dendritic cells. , 2007, Cancer research.

[66]  C. Wagener,et al.  CEACAM1, an adhesion molecule of human granulocytes, is fucosylated by fucosyltransferase IX and interacts with DC-SIGN of dendritic cells via Lewis x residues. , 2006, Glycobiology.

[67]  T. Yonezawa,et al.  Dcir deficiency causes development of autoimmune diseases in mice due to excess expansion of dendritic cells , 2008, Nature Medicine.

[68]  M. Nussenzweig,et al.  Normal Host Defense during Systemic Candidiasis in Mannose Receptor-Deficient Mice , 2003, Infection and Immunity.

[69]  N. Olson,et al.  Dendritic-cell-associated C-type lectin 2 (DCAL-2) alters dendritic-cell maturation and cytokine production. , 2006, Blood.

[70]  R. Steinman,et al.  In Vivo Targeting of Antigens to Maturing Dendritic Cells via the DEC-205 Receptor Improves T Cell Vaccination , 2004, The Journal of experimental medicine.

[71]  C. Figdor,et al.  Effective induction of naive and recall T-cell responses by targeting antigen to human dendritic cells via a humanized anti-DC-SIGN antibody. , 2005, Blood.

[72]  D. Kasper,et al.  Polysaccharide Processing and Presentation by the MHCII Pathway , 2004, Cell.

[73]  Sankar Ghosh,et al.  Recognition and signaling by toll-like receptors. , 2006, Annual review of cell and developmental biology.

[74]  A. Bringmann,et al.  hDectin-1 is involved in uptake and cross-presentation of cellular antigens. , 2008, Blood.

[75]  A. Steinkasserer,et al.  DC-SIGN and DC-SIGNR Interact with the Glycoprotein of Marburg Virus and the S Protein of Severe Acute Respiratory Syndrome Coronavirus , 2004, Journal of Virology.

[76]  Gemma L. J. Fuller,et al.  The C-type Lectin Receptors CLEC-2 and Dectin-1, but Not DC-SIGN, Signal via a Novel YXXL-dependent Signaling Cascade* , 2007, Journal of Biological Chemistry.

[77]  Á. Corbí,et al.  C-Type Lectins DC-SIGN and L-SIGN Mediate Cellular Entry by Ebola Virus in cis and in trans , 2002, Journal of Virology.

[78]  T. Geijtenbeek,et al.  Interactions of DC‐SIGN with Mac‐1 and CEACAM1 regulate contact between dendritic cells and neutrophils , 2005, FEBS letters.

[79]  Douglas S Kwon,et al.  DC-SIGN, a Dendritic Cell–Specific HIV-1-Binding Protein that Enhances trans-Infection of T Cells , 2000, Cell.

[80]  C. Figdor,et al.  Identification of DC-SIGN, a Novel Dendritic Cell–Specific ICAM-3 Receptor that Supports Primary Immune Responses , 2000, Cell.

[81]  K. Drickamer C-type lectin-like domains. , 1999, Current opinion in structural biology.

[82]  T. Geijtenbeek,et al.  Differential regulation of C-type lectin expression on tolerogenic dendritic cell subsets. , 2006, Immunobiology.

[83]  S. Gordon,et al.  Dectin-1 uses novel mechanisms for yeast phagocytosis in macrophages. , 2004, Blood.

[84]  J. Ruland,et al.  Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity , 2006, Nature.

[85]  Shizuo Akira,et al.  Collaborative Induction of Inflammatory Responses by Dectin-1 and Toll-like Receptor 2 , 2003, The Journal of experimental medicine.

[86]  R. Medzhitov,et al.  Regulation of Phagosome Maturation by Signals from Toll-Like Receptors , 2004, Science.

[87]  G. Schütz,et al.  Lipopolysaccharide and ceramide docking to CD14 provokes ligand‐specific receptor clustering in rafts , 2001, European journal of immunology.

[88]  T. Geijtenbeek,et al.  Neutrophils mediate immune modulation of dendritic cells through glycosylation-dependent interactions between Mac-1 and DC-SIGN , 2005, The Journal of experimental medicine.

[89]  Maureen E. Taylor,et al.  Characterization of carbohydrate recognition by langerin, a C-type lectin of Langerhans cells. , 2003, Glycobiology.

[90]  A. Simmons,et al.  Activation of the lectin DC-SIGN induces an immature dendritic cell phenotype triggering Rho-GTPase activity required for HIV-1 replication , 2007, Nature Immunology.

[91]  M. Richard,et al.  Granulocyte macrophage-colony stimulating factor reduces the affinity of SHP-2 for the ITIM of CLECSF6 in neutrophils: a new mechanism of action for SHP-2. , 2006, Molecular immunology.

[92]  R. Doms,et al.  Diversity of receptors binding HIV on dendritic cell subsets , 2002, Nature Immunology.

[93]  Natsuko Nakamura,et al.  Glycosylation-Dependent Interactions of C-Type Lectin DC-SIGN with Colorectal Tumor-Associated Lewis Glycans Impair the Function and Differentiation of Monocyte-Derived Dendritic Cells1 , 2008, The Journal of Immunology.