Top

Published in:

Open Access 01-07-2009 | Symposium Paper

Innate signaling by the C-type lectin DC-SIGN dictates immune responses

Authors: Jeroen den Dunnen, Sonja I. Gringhuis, Teunis B. H. Geijtenbeek

Published in: Cancer Immunology, Immunotherapy | Issue 7/2009

Abstract

Effective immune responses depend on the recognition of pathogens by dendritic cells (DCs) through pattern recognition receptors (PRRs). These receptors induce specific signaling pathways that lead to the induction of immune responses against the pathogens. It is becoming evident that C-type lectins are also important PRRs. In particular, the C-type lectin DC-SIGN has emerged as a key player in the induction of immune responses against numerous pathogens by modulating TLR-induced activation. Recent reports have begun to elucidate the molecular mechanisms underlying these immune responses. Upon pathogen binding, DC-SIGN induces an intracellular signaling pathway with a central role for the serine/threonine kinase Raf-1. For several pathogens that interact with DC-SIGN, including Mycobacterium tuberculosis and HIV-1, Raf-1 activation leads to acetylation of NF-κB subunit p65, which induces specific gene transcription profiles. In addition, other DC-SIGN-ligands induce different signaling pathways downstream of Raf-1, indicating that DC-SIGN-signaling is tailored to the pathogen. In this review we will discuss in detail the current knowledge about DC-SIGN signaling and its implications on immunity.

Appelmelk BJ, Van Die I, van Vliet SJ, Vandenbroucke-Grauls CM, Geijtenbeek TB, van Kooyk Y (2003) Cutting edge: carbohydrate profiling identifies new pathogens that interact with dendritic cell-specific ICAM-3-grabbing nonintegrin on dendritic cells. J Immunol 170:1635PubMed

Barreiro LB, Neyrolles O, Babb CL, Tailleux L, Quach H, McElreavey K, Helden PD, Hoal EG, Gicquel B, Quintana-Murci L (2006) Promoter variation in the DC-SIGN-encoding gene CD209 is associated with tuberculosis. PLoS Med 3:e20PubMedCrossRef

Bergman MP, Engering A, Smits HH, van Vliet SJ, van Bodegraven AA, Wirth HP, Kapsenberg ML, Vandenbroucke-Grauls CM, van Kooyk Y, Appelmelk BJ (2004) Helicobacter pylori modulates the T helper cell 1/T helper cell 2 balance through phase-variable interaction between lipopolysaccharide and DC-SIGN. J Exp Med 200:979PubMedCrossRef

Bernhard OK, Lai J, Wilkinson J, Sheil MM, Cunningham AL (2004) Proteomic analysis of DC-SIGN on dendritic cells detects tetramers required for ligand binding but no association with CD4. J Biol Chem 279:51828PubMedCrossRef

Caparros E, Munoz P, Sierra-Filardi E, Serrano-Gomez D, Puig-Kroger A, Rodriguez-Fernandez JL, Mellado M, Sancho J, Zubiaur M, Corbi AL (2006) DC-SIGN ligation on dendritic cells results in ERK and PI3K activation and modulates cytokine production. Blood 107:3950PubMedCrossRef

Cunningham AL, Harman AN, Donaghy H (2007) DC-SIGN ‘AIDS’ HIV immune evasion and infection. Nat Immunol 8:556PubMedCrossRef

Das S, Banerjee G, DePonte K, Marcantonio N, Kantor FS, Fikrig E (2001) Salp25D, an Ixodes scapularis antioxidant, is 1 of 14 immunodominant antigens in engorged tick salivary glands. J Infect Dis 184:1056PubMedCrossRef

Engering A, Geijtenbeek TB, van Vliet SJ, Wijers M, van Liempt E, Demaurex N, Lanzavecchia A, Fransen J, Figdor CG, Piguet V, van Kooyk Y (2002) The dendritic cell-specific adhesion receptor DC-SIGN internalizes antigen for presentation to T cells. J Immunol 168:2118PubMed

Fuller GL, Williams JA, Tomlinson MG, Eble JA, Hanna SL, Pohlmann S, Suzuki-Inoue K, Ozaki Y, Watson SP, Pearce AC (2007) The C-type lectin receptors CLEC-2 and Dectin-1, but not DC-SIGN, signal via a novel YXXL-dependent signaling cascade. J Biol Chem 282:12397PubMedCrossRef

10.

Gantner BN, Simmons RM, Canavera SJ, Akira S, Underhill DM (2003) Collaborative induction of inflammatory responses by dectin-1 and Toll-like receptor 2. J Exp Med 197:1107PubMedCrossRef

11.

Gantner BN, Simmons RM, Underhill DM (2005) Dectin-1 mediates macrophage recognition of Candida albicans yeast but not filaments. EMBO J 24:1277PubMedCrossRef

12.

Geijtenbeek TB, Krooshoop DJ, Bleijs DA, van Vliet SJ, van Duijnhoven GC, Grabovsky V, Alon R, Figdor CG, van Kooyk Y (2000) DC-SIGN-ICAM-2 interaction mediates dendritic cell trafficking. Nat Immunol 1:353PubMedCrossRef

13.

Geijtenbeek TB, Kwon DS, Torensma R, van Vliet SJ, van Duijnhoven GC, Middel J, Cornelissen IL, Nottet HS, KewalRamani VN, Littman DR, Figdor CG, van Kooyk Y (2000) DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. Cell 100:587PubMedCrossRef

14.

Geijtenbeek TB, van Vliet SJ, Koppel EA, Sanchez-Hernandez M, Vandenbroucke-Grauls CM, Appelmelk B, van Kooyk Y (2003) Mycobacteria target DC-SIGN to suppress dendritic cell function. J Exp Med 197:7PubMedCrossRef

15.

Geijtenbeek TBH, Torensma R, van Vliet SJ, van Duijnhoven GCF, Adema GJ, van Kooyk Y, Figdor CG (2000) Identification of DC-SIGN, a novel dendritic cell-specific ICAM-3 receptor that supports primary immune responses. Cell 100:575PubMedCrossRef

16.

Gilchrist M, Thorsson V, Li B, Rust AG, Korb M, Roach JC, Kennedy K, Hai T, Bolouri H, Aderem A (2006) Systems biology approaches identify ATF3 as a negative regulator of Toll-like receptor 4. Nature 441:173PubMedCrossRef

17.

Granelli-Piperno A, Pritsker A, Pack M, Shimeliovich I, Arrighi JF, Park CG, Trumpfheller C, Piguet V, Moran TM, Steinman RM (2005) Dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin/CD209 is abundant on macrophages in the normal human lymph node and is not required for dendritic cell stimulation of the mixed leukocyte reaction. J Immunol 175:4265PubMed

18.

Gringhuis SI, den Dunnen J, Litjens M, van het Hof B, van Kooyk Y, Geijtenbeek TBH (2007) C-type lectin DC-SIGN modulates toll-like receptor signaling via Raf-1 kinase-dependent acetylation of transcription factor NF-kappa B. Immunity 26:605PubMedCrossRef

19.

Gross O, Gewies A, Finger K, Schafer M, Sparwasser T, Peschel C, Forster I, Ruland J (2006) Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity. Nature 442:651PubMedCrossRef

20.

Hayden MS, Ghosh S (2004) Signaling to NF-kappaB. Genes Dev 18:2195PubMedCrossRef

21.

Hodges A, Sharrocks K, Edelmann M, Baban D, Moris A, Schwartz O, Drakesmith H, Davies K, Kessler B, McMichael A, Simmons A (2007) Activation of the lectin DC-SIGN induces an immature dendritic cell phenotype triggering Rho-GTPase activity required for HIV-1 replication. Nat Immunol 8:569PubMedCrossRef

22.

Hovius JW, de Jong MA, den Dunnen J, Litjens M, Fikrig E, van der Poll T, Gringhuis SI, Geijtenbeek TB (2008) Salp15 binding to DC-SIGN inhibits cytokine expression by impairing both nucleosome remodeling and mRNA stabilization. PLoS Pathog 4:e31PubMedCrossRef

23.

Janeway CA, Medzhitov R (2002) Innate immune recognition. Annu Rev Immunol 20:197PubMedCrossRef

24.

Juncadella IJ, Garg R, Ananthnarayanan SK, Yengo CM, Anguita J (2007) T-cell signaling pathways inhibited by the tick saliva immunosuppressor, Salp15. FEMS Immunol Med Microbiol 49:433PubMedCrossRef

25.

Kolch W (2005) Coordinating ERK/MAPK signalling through scaffolds and inhibitors. Nat Rev Mol Cell Biol 6:827PubMedCrossRef

26.

Lee B, Leslie G, Soilleux E, O’Doherty U, Baik S, Levroney E, Flummerfelt K, Swiggard W, Coleman N, Malim M, Doms RW (2001) cis Expression of DC-SIGN allows for more efficient entry of human and simian immunodeficiency viruses via CD4 and a coreceptor. J Virol 75:12028PubMedCrossRef

27.

Lee MS, Kim YJ (2007) Signaling pathways downstream of pattern-recognition receptors and their cross talk. Annu Rev Biochem 76:447PubMedCrossRef

28.

Lowell CA (2004) Src-family kinases: rheostats of immune cell signaling. Mol Immunol 41:631PubMedCrossRef

29.

McDonald D, Wu L, Bohks SM, KewalRamani VN, Unutmaz D, Hope TJ (2003) Recruitment of HIV and its receptors to dendritic cell-T cell junctions. Science 300:1295PubMedCrossRef

30.

Mitchell DA, Fadden AJ, Drickamer K (2001) A novel mechanism of carbohydrate recognition by the C-type lectins DC- SIGN and DC-SIGNR. Subunit organization and binding to multivalent ligands. J Biol Chem 276:28939PubMedCrossRef

31.

Nagaoka K, Takahara K, Tanaka K, Yoshida H, Steinman RM, Saitoh S, kashi-Takamura S, Miyake K, Kang YS, Park CG, Inaba K (2005) Association of SIGNR1 with TLR4-MD-2 enhances signal transduction by recognition of LPS in gram-negative bacteria. Int Immunol 17:827PubMedCrossRef

32.

Ouaaz F, Arron J, Zheng Y, Choi Y, Beg AA (2002) Dendritic cell development and survival require distinct NF-kappaB subunits. Immunity 16:257PubMedCrossRef

33.

Ramamoorthi N, Narasimhan S, Pal U, Bao F, Yang XF, Fish D, Anguita J, Norgard MV, Kantor FS, Anderson JF, Koski RA, Fikrig E (2005) The Lyme disease agent exploits a tick protein to infect the mammalian host. Nature 436:573PubMedCrossRef

34.

Robinson MJ, Sancho D, Slack EC, LeibundGut-Landmann S, Sousa CRE (2006) Myeloid C-type lectins in innate immunity. Nat Immunol 7:1258PubMedCrossRef

35.

Rogers NC, Slack EC, Edwards AD, Nolte MA, Schulz O, Schweighoffer E, Williams DL, Gordon S, Tybulewicz VL, Brown GD, Sousa ReisE (2005) Syk-dependent cytokine induction by Dectin-1 reveals a novel pattern recognition pathway for C type lectins. Immunity 22:507PubMedCrossRef

36.

Schaefer M, Reiling N, Fessler C, Stephani J, Taniuchi I, Hatam F, Yildirim AO, Fehrenbach H, Walter K, Ruland J, Wagner H, Ehlers S, Sparwasser T (2008) Decreased pathology and prolonged survival of human DC-SIGN transgenic mice during mycobacterial infection. J Immunol 180:6836PubMed

37.

Shan M, Klasse PJ, Banerjee K, Dey AK, Iyer SP, Dionisio R, Charles D, Campbell-Gardener L, Olson WC, Sanders RW, Moore JP (2007) HIV-1 gp120 mannoses induce immunosuppressive responses from dendritic cells. PLoS Pathog 3:e169PubMedCrossRef

38.

Shreffler WG, Castro RR, Kucuk ZY, Charlop-Powers Z, Grishina G, Yoo S, Burks AW, Sampson HA (2006) The major glycoprotein allergen from Arachis hypogaea, Ara h 1, is a ligand of dendritic cell-specific ICAM-grabbing nonintegrin and acts as a Th2 adjuvant in vitro. J Immunol 177:3677PubMed

39.

Smith AL, Ganesh L, Leung K, Jongstra-Bilen J, Jongstra J, Nabel GJ (2007) Leukocyte-specific protein 1 interacts with DC-SIGN and mediates transport of HIV to the proteasome in dendritic cells. J Exp Med 204:421PubMedCrossRef

40.

Smits HH, Engering A, van der Kleij D, de Jong EC, Schipper K, van Capel TM, Zaat BA, Yazdanbakhsh M, Wierenga EA, van Kooyk Y, Kapsenberg ML (2005) Selective probiotic bacteria induce IL-10-producing regulatory T cells in vitro by modulating dendritic cell function through dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin. J Allergy Clin Immunol 115:1260PubMedCrossRef

41.

Steeghs L, van Vliet SJ, Uronen-Hansson H, van Mourik A, Engering A, Sanchez-Hernandez M, Klein N, Callard R, van Putten JP, van der LP, van Kooyk Y, van de Winkel JG (2006) Neisseria meningitidis expressing lgtB lipopolysaccharide targets DC-SIGN and modulates dendritic cell function. Cell Microbiol 8:316PubMedCrossRef

42.

Takeda K, Akira S (2004) TLR signaling pathways. Semin Immunol 16:3PubMedCrossRef

43.

Valera I, Fernandez N, Trinidad AG, Alonso S, Brown GD, Alonso A, Crespo MS (2008) Costimulation of dectin-1 and DC-SIGN triggers the arachidonic acid cascade in human monocyte-derived dendritic cells. J Immunol 180:5727PubMed

44.

van Kooyk Y, Geijtenbeek TB (2003) DC-SIGN: escape mechanism for pathogens. Nat Rev Immunol 3:697PubMedCrossRef

45.

van Vliet SJ, den Dunnen J, Gringhuis SI, Geijtenbeek TB, van Kooyk Y (2007) Innate signaling and regulation of dendritic cell immunity. Curr Opin Immunol 19:435PubMedCrossRef

46.

Vannberg FO, Chapman SJ, Khor CC, Tosh K, Floyd S, Jackson-Sillah D, Crampin A, Sichali L, Bah B, Gustafson P, Aaby P, McAdam KP, Bah-Sow O, Lienhardt C, Sirugo G, Fine P, Hill AV (2008) CD209 genetic polymorphism and tuberculosis disease. PLoS ONE 3:e1388PubMedCrossRef

47.

Vermeulen L, de Wilde G, van Damme P, Vanden Berghe W, Haegeman G (2003) Transcriptional activation of the NF-kappaB p65 subunit by mitogen- and stress-activated protein kinase-1 (MSK1). EMBO J 22:1313PubMedCrossRef

48.

Wellbrock C, Karasarides M, Marais R (2004) The RAF proteins take centre stage. Nat Rev Mol Cell Biol 5:875PubMedCrossRef

49.

Zhong HH, May MJ, Jimi E, Ghosh S (2002) The phosphorylation status of nuclear NF-kappa B determines its association with CBP/p300 or HDAC-1. Mol Cell 9:625PubMedCrossRef

Title: Innate signaling by the C-type lectin DC-SIGN dictates immune responses
Authors: Jeroen den Dunnen
Sonja I. Gringhuis
Teunis B. H. Geijtenbeek
Publication date: 01-07-2009
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 7/2009
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-008-0615-1

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 7/2009

Anti-ganglioside anti-idiotypic monoclonal antibody-based cancer vaccine induces apoptosis and antiangiogenic effect in a metastatic lung carcinoma

A novel phosphorylated STAT3 inhibitor enhances T cell cytotoxicity against melanoma through inhibition of regulatory T cells

Phenotypic and functional alterations of Vγ2Vδ2 T cell subsets in patients with active nasopharyngeal carcinoma

Vaccination strategies in patients with renal cell carcinoma

Peroxisome proliferator-activated receptor gamma overexpression and knockdown: impact on human B cell lymphoma proliferation and survival

Polyinosinic polycytidylic acid prevents efficient antigen expression after mRNA electroporation of clinical grade dendritic cells

Keynote webinar | Spotlight on antibody–drug conjugates in cancer