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The DAP12-Associated Myeloid C-Type Lectin 5A (CLEC5A)

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C-Type Lectin Receptors in Immunity

Abstract

Innate immunity is the first line of host defense mechanism against pathogen invasion. In order to recognize various pathogen-associated molecular patterns, myeloid cells express abundant innate immunity receptors on cell surface to recognize diverse pathogen-associated molecular patterns (PAMPs). Toll-like receptors (TLRs) are the most well-characterized innate immunity receptors for pattern recognition, and activation of TLRs triggers the MyD88- and TRIF-dependent pathways to induce the secretion of pro-inflammatory cytokines and interferons (Akira and Takeda 2004; Athman and Philpott 2004). In addition to TLRs, natural killer cells and myeloid cells, which are the key players in innate immunity, recognize glycan and non-glycan structures on pathogen surface via the C-type lectin receptors (denoted as CLRs), which are the most abundant lectins in human genome. Among the myeloid CLRs, the spleen tyrosine kinase (Syk)-coupled C-type lectin receptors (Syk-CLRs) have been shown to play critical roles in host defense against pathogen invasion (Osorio et al. 2011; Sancho et al. 2012). Here, we discuss the potential roles of CLEC5A, also known as “myeloid DAP12-associating lectin-1 (MDL-1),” in host defense and autoimmunity. We would also discuss the impact of dual recognition by CLEC5A and TLRs in future study of host-pathogen interaction.

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References

  • Akira S, Takeda K (2004) Toll-like receptor signalling. Nat Rev Immunol 4:499–511

    Article  CAS  PubMed  Google Scholar 

  • Athman R, Philpott D (2004) Innate immunity via toll-like receptors and Nod proteins. Curr Opin Microbiol 7:25–32

    Article  CAS  PubMed  Google Scholar 

  • Bakker AB, Baker E, Sutherland GR, Phillips JH, Lanier LL (1999) Myeloid DAP12-associating lectin (MDL)-1 is a cell surface receptor involved in the activation of myeloid cells. Proc Natl Acad Sci U S A 96:9792–9796

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Batliner J et al (2011) CLEC5A (MDL-1) is a novel PU.1 transcriptional target during myeloid differentiation. Mol Immunol 48:714–719

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen YC, Wang SY (2002) Activation of terminally differentiated human monocytes/macrophages by dengue virus: productive infection, hierarchical production of innate cytokines and chemokines, and the synergistic effect of lipopolysaccharide. J Virol 76:9877–9887

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen ST et al (2008) CLEC5A is critical for dengue-virus-induced lethal disease. Nature 453:672–676

    Article  CAS  PubMed  Google Scholar 

  • Chen ST et al (2012) CLEC5A regulates Japanese encephalitis virus-induced neuroinflammation and lethality. PLoS Pathog 8:e1002655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen DY et al (2014) A potential role of myeloid DAP12-associating lectin (MDL)-1 in the regulation of inflammation in rheumatoid arthritis patients. PLoS One 9:e86105

    Article  PubMed  PubMed Central  Google Scholar 

  • Cheung R et al (2011) Activation of MDL-1 (CLEC5A) on immature myeloid cells triggers lethal shock in mice. J Clin Invest 121:4446–4461

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Davey MS et al (2011) Failure to detect production of IL-10 by activated human neutrophils. Nat Immunol 12:1017–1018; author reply 1018-1020

    Article  CAS  PubMed  Google Scholar 

  • Esnault S et al (2013) Identification of genes expressed by human airway eosinophils after an in vivo allergen challenge. PLoS One 8:e67560

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gomes AL et al (2010) Classification of dengue fever patients based on gene expression data using support vector machines. PLoS One 5:e11267

    Article  PubMed  PubMed Central  Google Scholar 

  • Gramberg T et al (2006) Impact of polymorphisms in the DC-SIGNR neck domain on the interaction with pathogens. Virology 347:354–363

    Article  CAS  PubMed  Google Scholar 

  • Hoke CH et al (1988) Protection against Japanese encephalitis by inactivated vaccines. N Engl J Med 319:608–614

    Article  CAS  PubMed  Google Scholar 

  • Hollidge BS, Gonzalez-Scarano F, Soldan SS (2010) Arboviral encephalitides: transmission, emergence, and pathogenesis. J Neuroimmune Pharmacol 5:428–442

    Article  PubMed  PubMed Central  Google Scholar 

  • Hsu TL et al (2009) Profiling carbohydrate-receptor interaction with recombinant innate immunity receptor-Fc fusion proteins. J Biol Chem 284:34479–34489

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Inui M et al (2009) Signal adaptor DAP10 associates with MDL-1 and triggers osteoclastogenesis in cooperation with DAP12. Proc Natl Acad Sci U S A 106:4816–4821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ishikawa E et al (2009) Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle. J Exp Med 206:2879–2888

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jessie K, Fong MY, Devi S, Lam SK, Wong KT (2004) Localization of dengue virus in naturally infected human tissues, by immunohistochemistry and in situ hybridization. J Infect Dis 189:1411–1418

    Article  PubMed  Google Scholar 

  • Joyce-Shaikh B et al (2010) Myeloid DAP12-associating lectin (MDL)-1 regulates synovial inflammation and bone erosion associated with autoimmune arthritis. J Exp Med 207:579–589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kanneganti TD (2010) Central roles of NLRs and inflammasomes in viral infection. Nat Rev Immunol 10:688–698

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kasten KR, Muenzer JT, Caldwell CC (2010) Neutrophils are significant producers of IL-10 during sepsis. Biochem Biophys Res Commun 393:28–31

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim M et al (2012) Herpes simplex virus antigens directly activate NK cells via TLR2, thus facilitating their presentation to CD4 T lymphocytes. J Immunol 188:4158–4170

    Article  CAS  PubMed  Google Scholar 

  • Ku CC et al (1994) Homologous and heterologous neutralization antibody responses after immunization with Japanese encephalitis vaccine among Taiwan children. J Med Virol 44:122–131

    Article  CAS  PubMed  Google Scholar 

  • Kurt-Jones EA et al (2000) Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus. Nat Immunol 1:398–401

    Article  CAS  PubMed  Google Scholar 

  • Lee IK, Liu JW, Yang KD (2005) Clinical characteristics and risk factors for concurrent bacteremia in adults with dengue hemorrhagic fever. Am J Trop Med Hyg 72:221–226

    PubMed  Google Scholar 

  • Mackenzie JS, Gubler DJ, Petersen LR (2004) Emerging flaviviruses: the spread and resurgence of Japanese encephalitis, West Nile and dengue viruses. Nat Med 10:S98–S109

    Article  CAS  PubMed  Google Scholar 

  • Mikula I Jr, Pastorekova S, Mikula I Sr (2010) Toll-like receptors in immune response to the viral infections. Acta Virol 54:231–245

    Article  CAS  PubMed  Google Scholar 

  • Mukhopadhyay S, Kuhn RJ, Rossmann MG (2005) A structural perspective of the flavivirus life cycle. Nat Rev Microbiol 3:13–22

    Article  CAS  PubMed  Google Scholar 

  • Nattermann J et al (2006) The tandem-repeat polymorphism of the DC-SIGNR gene in HCV infection. J Viral Hepat 13:42–46

    Article  CAS  PubMed  Google Scholar 

  • Netea MG, Kullberg BJ, Van der Meer JW (2000) Circulating cytokines as mediators of fever. Clin Infect Dis 31(Suppl 5):S178–S184

    Article  CAS  PubMed  Google Scholar 

  • Olsen SJ et al (2010) Japanese encephalitis virus remains an important cause of encephalitis in Thailand. Int J Infect Dis 14:e888–e892

    Article  PubMed  Google Scholar 

  • Osorio F, Reis E, Sousa C (2011) Myeloid C-type lectin receptors in pathogen recognition and host defense. Immunity 34:651–664

    Article  CAS  PubMed  Google Scholar 

  • Pokidysheva E et al (2006) Cryo-EM reconstruction of dengue virus in complex with the carbohydrate recognition domain of DC-SIGN. Cell 124:485–493

    Article  CAS  PubMed  Google Scholar 

  • Rabes A et al (2015) The C-type lectin receptor Mincle binds to Streptococcus pneumoniae but plays a limited role in the anti-pneumococcal innate immune response. PLoS One 10:e0117022

    Article  PubMed  PubMed Central  Google Scholar 

  • Reske A, Pollara G, Krummenacher C, Katz DR, Chain BM (2008) Glycoprotein-dependent and TLR2-independent innate immune recognition of herpes simplex virus-1 by dendritic cells. J Immunol 180:7525–7536

    Article  CAS  PubMed  Google Scholar 

  • Saijo S et al (2007) Dectin-1 is required for host defense against Pneumocystis carinii but not against Candida albicans. Nat Immunol 8:39–46

    Article  CAS  PubMed  Google Scholar 

  • Sancho D, Reis E, Sousa C (2012) Signaling by myeloid C-type lectin receptors in immunity and homeostasis. Annu Rev Immunol 30:491–529

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schroder K, Tschopp J (2010) The inflammasomes. Cell 140:821–832

    Article  CAS  PubMed  Google Scholar 

  • Taylor PR et al (2007) Dectin-1 is required for beta-glucan recognition and control of fungal infection. Nat Immunol 8:31–38

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tiegs G, Hentschel J, Wendel A (1992) A T cell-dependent experimental liver injury in mice inducible by concanavalin A. J Clin Invest 90:196–203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tung YT, Wu MF, Wang GJ, Hsieh SL (2014) Nanostructured electrochemical biosensor for the detection of the weak binding between the dengue virus and the CLEC5A receptor. Nanomed: Nanotechnol Biol Med 10:1335–1341

    CAS  Google Scholar 

  • Varki A, Cummings RD, Esko JD et al (2009) Chapter 31: C-type lectins. In: Essentials of glycobiology, Cold Spring Harbor Press, New York, USA

    Google Scholar 

  • Watson AA, O’Callaghan CA (2010) Crystallization and X-ray diffraction analysis of human CLEC5A (MDL-1), a dengue virus receptor. Acta Crystallogr Sect F: Struct Biol Cryst Commun 66:29–31

    Article  CAS  Google Scholar 

  • Watson AA et al (2011) Structural flexibility of the macrophage dengue virus receptor CLEC5A: implications for ligand binding and signaling. J Biol Chem 286:24208–24218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weaver SC, Barrett AD (2004) Transmission cycles, host range, evolution and emergence of arboviral disease. Nat Rev Microbiol 2:789–801

    Article  CAS  PubMed  Google Scholar 

  • Wells CA et al (2008) The macrophage-inducible C-type lectin, mincle, is an essential component of the innate immune response to Candida albicans. J Immunol 180:7404–7413

    Article  CAS  PubMed  Google Scholar 

  • Wilder-Smith A, Schwartz E (2005) Dengue in travelers. N Engl J Med 353:924–932

    Article  CAS  PubMed  Google Scholar 

  • Wu MF, Chen ST, Hsieh SL (2013a) Distinct regulation of dengue virus-induced inflammasome activation in human macrophage subsets. J Biomed Sci 20:36

    Article  PubMed  PubMed Central  Google Scholar 

  • Wu MF et al (2013b) CLEC5A is critical for dengue virus-induced inflammasome activation in human macrophages. Blood 121:95–106

    Article  CAS  PubMed  Google Scholar 

  • Xavier-Carvalho C et al (2013) Single nucleotide polymorphisms in candidate genes and dengue severity in children: a case-control, functional and meta-analysis study. Infect Genet Evol: J Mol Epidemiol Evol Genet Infect Dis 20:197–205

    Article  CAS  Google Scholar 

  • Xin YY, Ming ZG, Peng GY, Jian A, Min LH (1988) Safety of a live-attenuated Japanese encephalitis virus vaccine (SA14-14-2) for children. Am J Trop Med Hyg 39:214–217

    CAS  PubMed  Google Scholar 

  • Zhang X, Majlessi L, Deriaud E, Leclerc C, Lo-Man R (2009) Coactivation of Syk kinase and MyD88 adaptor protein pathways by bacteria promotes regulatory properties of neutrophils. Immunity 31:761–771

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by the National Science Council (NSC 103-2321-B-001-044 and NSC 103-2320-B-001-010-MY3) and Summit and Thematic Research Project (AS-101-TP-B06-2) of Academia Sinica.

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Authors and Affiliations

  1. Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei, 115, Taiwan

    Shie-Liang Hsieh

  2. Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan

    Shie-Liang Hsieh

  3. Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan

    Shie-Liang Hsieh

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  1. Shie-Liang Hsieh
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Correspondence to Shie-Liang Hsieh .

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Editors and Affiliations

  1. Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan

    Sho Yamasaki

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Hsieh, SL. (2016). The DAP12-Associated Myeloid C-Type Lectin 5A (CLEC5A). In: Yamasaki, S. (eds) C-Type Lectin Receptors in Immunity. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56015-9_3

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