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C-type lectins: their network and roles in pathogen recognition and immunity

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Abstract

C-type lectins (CTLs) represent the most complex family of animal/human lectins that comprises 17 different groups. During evolution, CTLs have developed by diversification to cover a broad range of glycan ligands. However, ligand binding by CTLs is not necessarily restricted to glycans as some CTLs also bind to proteins, lipids, inorganic molecules, or ice crystals. CTLs share a common fold that harbors a Ca2+ for contact to the sugar and about 18 invariant residues in a phylogenetically conserved pattern. In vertebrates, CTLs have numerous functions, including serum glycoprotein homeostasis, pathogen sensing, and the initiation of immune responses. Myeloid CTLs in innate immunity are mainly expressed by antigen-presenting cells and play a prominent role in the recognition of a variety of pathogens such as fungi, bacteria, viruses, and parasites. However, myeloid CTLs such as the macrophage inducible CTL (Mincle) or Clec-9a may also bind to self-antigens and thus contribute to immune homeostasis. While some CTLs induce pro-inflammatory responses and thereby lead to activation of adaptive immune responses, other CTLs act as inhibitory receptors and dampen cellular functions. Since CTLs are key players in pathogen recognition and innate immunity, targeting CTLs may be a promising strategy for cell-specific delivery of drugs or vaccine antigens and to modulate immune responses.

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References

  • Aarnoudse CA, Bax M, Sánchez-Hernández M, García-Vallejo JJ, van Kooyk Y (2008) Glycan modification of the tumor antigen gp100 targets DC-SIGN to enhance dendritic cell induced antigen presentation to T cells. Int J Cancer 122(4):839–846

    Article  CAS  PubMed  Google Scholar 

  • André S, Kaltner H, Kayser K, Murphy PV, Gabius HJ (2016) Merging carbohydrate chemistry with lectin histochemistry to study inhibition of lectin binding by glycoclusters in the natural tissue context. Histochem Cell Biol 145(2):185–199

    Article  PubMed  CAS  Google Scholar 

  • Angiari S (2015) Selectin-mediated leukocyte trafficking during the development of autoimmune disease. Autoimmun Rev 14(11):984–995

    Article  CAS  PubMed  Google Scholar 

  • Arnáiz B, Martínez-Ávila O, Falcon-Perez JM, Penadés S (2012) Cellular uptake of gold nanoparticles bearing HIV gp120 oligomannosides. Bioconjug Chem 23(4):814–825

    Article  PubMed  CAS  Google Scholar 

  • Barreiro LB, Quach H, Krahenbuhl J, Khaliq S, Mohyuddin A, Mehdi SQ, Gicquel B, Neyrolles O, Quintana-Murci L (2006) DC-SIGN interacts with Mycobacterium leprae but sequence variation in this lectin is not associated with leprosy in the Pakistani population. Hum Immunol 67(1–2):102–107

    Article  CAS  PubMed  Google Scholar 

  • Barrow AD, Trowsdale J (2006) You say ITAM and I say ITIM, let’s call the whole thing off: the ambiguity of immunoreceptor signalling. Eur J Immunol 36(7):1646–1653

    Article  CAS  PubMed  Google Scholar 

  • Bernardes GJ, Kikkeri R, Maglinao M, Laurino P, Collot M, Hong SY, Lepenies B, Seeberger PH (2010) Design, synthesis and biological evaluation of carbohydrate-functionalized cyclodextrins and liposomes for hepatocyte-specific targeting. Org Biomol Chem 8(21):4987–4996

    Article  CAS  PubMed  Google Scholar 

  • Bhide GP, Colley KJ (2017) Sialylation of N-glycans: mechanism, cellular compartmentalization and function. Histochem Cell Biol 147(2). doi:10.1007/s00418-016-1520-x

  • Bordet J, Gay F-P (1906) Sur les relations des sensibilisatrices avec l’alexine. Annales de L’Institut Pasteur 20:467–473

    Google Scholar 

  • Brzezicka K, Vogel U, Serna S, Johannssen T, Lepenies B, Reichardt NC (2016) Influence of core beta-1,2-xylosylation on glycoprotein recognition by murine C-type lectin receptors and its impact on dendritic cell targeting. ACS Chem Biol 11(8):2347–2356

    Article  CAS  PubMed  Google Scholar 

  • Carroll MV, Sim RB, Bigi F, Jakel A, Antrobus R, Mitchell DA (2010) Identification of four novel DC-SIGN ligands on Mycobacterium bovis BCG. Protein Cell 1(9):859–870

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chiodo F, Marradi M, Park J, Ram AF, Penades S, van Die I, Tefsen B (2014) Galactofuranose-coated gold nanoparticles elicit a pro-inflammatory response in human monocyte-derived dendritic cells and are recognized by DC-SIGN. ACS Chem Biol 9(2):383–389

    Article  CAS  PubMed  Google Scholar 

  • Corfield AP (2017) Protein glycosylation: a primer for histochemists and cell biologists. Histochem Cell Biol 147(2). doi:10.1007/s00418-016-1526-4

  • Cummings RD, McEver RP (2009) C-type lectins. In: Varki A, Cummings RD, Esko JD et al (eds) Essentials of glycobiology, 2nd edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor

    Google Scholar 

  • da Glória Sousa M, Reid DM, Schweighoffer E, Tybulewicz V, Ruland J, Langhorne J, Yamasaki S, Taylor PR, Almeida SR, Brown GD (2011) Restoration of pattern recognition receptor costimulation to treat chromoblastomycosis, a chronic fungal infection of the skin. Cell Host Microbe 9(5):436–443

    Article  PubMed Central  CAS  Google Scholar 

  • Dennehy KM, Ferwerda G, Faro-Trindade I, Pyz E, Willment JA, Taylor PR, Kerrigan A, Tsoni SV, Gordon S, Meyer-Wentrup F, Adema GJ, Kullberg BJ, Schweighoffer E, Tybulewicz V, Mora-Montes HM, Gow NA, Williams DL, Netea MG, Brown GD (2008) Syk kinase is required for collaborative cytokine production induced through Dectin-1 and Toll-like receptors. Eur J Immunol 38(2):500–506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Devi S, Rajakumara E, Ahmed N (2015) Induction of Mincle by Helicobacter pylori and consequent anti-inflammatory signaling denote a bacterial survival strategy. Sci Rep 5:15049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dobó J, Pál G, Cervenak L, Gál P (2016) The emerging roles of mannose-binding lectin-associated serine proteases (MASPs) in the lectin pathway of complement and beyond. Immunol Rev 274(1):98–111

    Article  PubMed  CAS  Google Scholar 

  • Drickamer K (1988) Two distinct classes of carbohydrate-recognition domains in animal lectins. J Biol Chem 263(20):9557–9560

    CAS  PubMed  Google Scholar 

  • Drickamer K, Fadden AJ (2002) Genomic analysis of C-type lectins. Biochem Soc Symp 69:59–72

    Article  CAS  Google Scholar 

  • Drickamer K, Taylor ME (2015) Recent insights into structures and functions of C-type lectins in the immune system. Curr Opin Struct Biol 34:26–34

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Drickamer K, Dordal MS, Reynolds L (1986) Mannose-binding proteins isolated from rat liver contain carbohydrate-recognition domains linked to collagenous tails. Complete primary structures and homology with pulmonary surfactant apoprotein. J Biol Chem 261(15):6878–6887

    CAS  PubMed  Google Scholar 

  • Drummond RA, Brown GD (2011) The role of Dectin-1 in the host defence against fungal infections. Curr Opin Microbiol 14(4):392–399

    Article  CAS  PubMed  Google Scholar 

  • Drummond RA, Brown GD (2013) Signalling C-type lectins in antimicrobial immunity. PLoS Pathog 9(7):e1003417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eriksson M, Johannssen T, von Smolinski D, Gruber AD, Seeberger PH, Lepenies B (2013) The C-type lectin receptor SIGNR3 binds to fungi present in commensal microbiota and influences immune regulation in experimental colitis. Front Immunol 4:196

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ferwerda B, Ferwerda G, Plantinga TS, Willment JA, van Spriel AB, Venselaar H, Elbers CC, Johnson MD, Cambi A, Huysamen C, Jacobs L, Jansen T, Verheijen K, Masthoff L, Morre SA, Vriend G, Williams DL, Perfect JR, Joosten LA, Wijmenga C, van der Meer JW, Adema GJ, Kullberg BJ, Brown GD, Netea MG (2009) Human Dectin-1 deficiency and mucocutaneous fungal infections. N Engl J Med 361(18):1760–1767

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Figdor CG, van Kooyk Y, Adema GJ (2002) C-type lectin receptors on dendritic cells and Langerhans cells. Nat Rev Immunol 2(2):77–84

    Article  CAS  PubMed  Google Scholar 

  • Foo SS, Reading PC, Jaillon S, Mantovani A, Mahalingam S (2015) Pentraxins and collectins: friend or foe during pathogen invasion? Trends Microbiol 23(12):799–811

    Article  CAS  PubMed  Google Scholar 

  • Fujikado N, Saijo S, Yonezawa T, Shimamori K, Ishii A, Sugai S, Kotaki H, Sudo K, Nose M, Iwakura Y (2008) Dcir deficiency causes development of autoimmune diseases in mice due to excess expansion of dendritic cells. Nat Med 14(2):176–180

    Article  CAS  PubMed  Google Scholar 

  • Gabius HJ (2015) The magic of the sugar code. Trends Biochem Sci 40(7):341

    Article  CAS  PubMed  Google Scholar 

  • Gabius H-J, Roth J (2017) An introduction to the sugar code. Histochem Cell Biol 147(2). doi:10.1007/s00418-016-1521-9

  • Gabius HJ, Kaltner H, Kopitz J, André S (2015) The glycobiology of the CD system: a dictionary for translating marker designations into glycan/lectin structure and function. Trends Biochem Sci 40(7):360–376

    Article  CAS  PubMed  Google Scholar 

  • Gabius HJ, Manning JC, Kopitz J, André S, Kaltner H (2016) Sweet complementarity: the functional pairing of glycans with lectins. Cell Mol Life Sci 73(10):1989–2016

    Article  CAS  PubMed  Google Scholar 

  • García-Vallejo JJ, Ambrosini M, Overbeek A, van Riel WE, Bloem K, Unger WW, Chiodo F, Bolscher JG, Nazmi K, Kalay H, van Kooyk Y (2013) Multivalent glycopeptide dendrimers for the targeted delivery of antigens to dendritic cells. Mol Immunol 53(4):387–397

    Article  PubMed  CAS  Google Scholar 

  • Garred P, Genster N, Pilely K, Bayarri-Olmos R, Rosbjerg A, Ma YJ, Skjoedt MO (2016) A journey through the lectin pathway of complement-MBL and beyond. Immunol Rev 274(1):74–97

    Article  CAS  PubMed  Google Scholar 

  • Ge MQ, Kokalari B, Flayer CH, Killingbeck SS, Redai IG, MacFarlane AW, Hwang JW, Kolupoti A, Kemeny DM, Campbell KS, Haczku A (2016) Cutting edge: role of NK cells and surfactant protein D in dendritic cell lymph node homing: effects of ozone exposure. J Immunol 196(2):553–557

    Article  CAS  PubMed  Google Scholar 

  • Geahlen RL (2014) Getting Syk: spleen tyrosine kinase as a therapeutic target. Trends Pharmacol Sci 35(8):414–422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Geijtenbeek TB, Gringhuis SI (2009) Signalling through C-type lectin receptors: shaping immune responses. Nat Rev Immunol 9(7):465–479

    Article  CAS  PubMed  Google Scholar 

  • Geijtenbeek TB, Gringhuis SI (2016) C-type lectin receptors in the control of T helper cell differentiation. Nat Rev Immunol 16(7):433–448

    Article  CAS  PubMed  Google Scholar 

  • Geijtenbeek TBH, Krooshoop DJEB, Bleijs DA, van Vliet SJ, van Duijnhoven GCF, Grabovsky V, Alon R, Figdor CG, van Kooyk Y (2000a) DC-SIGN-ICAM-2 interaction mediates dendritic cell trafficking. Nat Immunol 1(4):353–357

    Article  CAS  PubMed  Google Scholar 

  • Geijtenbeek TBH, 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 (2000b) DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. Cell 100(5):587–597

    Article  CAS  PubMed  Google Scholar 

  • Geijtenbeek TBH, Torensma R, van Vliet SJ, van Duijnhoven GCF, Adema GJ, van Kooyk Y, Figdor CG (2000c) Identification of DC-SIGN, a novel dendritic cell-specific ICAM-3 receptor that supports primary immune responses. Cell 100(5):575–585

    Article  CAS  PubMed  Google Scholar 

  • Geijtenbeek TBH, 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(1):7–17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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(7):4265–4273

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gready J, Zelensky AN (2009) Routes in lectin evolution: case study on the C-type lectin-like domains. In: Gabius HJ (ed) The sugar code: fundamentals of glycosciences. Wiley-VCH, Weinheim

    Google Scholar 

  • Gringhuis SI, den Dunnen J, Litjens M, van Het Hof B, van Kooyk Y, Geijtenbeek TB (2007) C-type lectin DC-SIGN modulates Toll-like receptor signaling via Raf-1 kinase-dependent acetylation of transcription factor NF-kappaB. Immunity 26(5):605–616

    Article  CAS  PubMed  Google Scholar 

  • Hansen SW, Ohtani K, Roy N, Wakamiya N (2016) The collectins CL-L1, CL-K1 and CL-P1, and their roles in complement and innate immunity. Immunobiology 221(10):1058–1067

    Article  CAS  PubMed  Google Scholar 

  • Hardison SE, Brown GD (2012) C-type lectin receptors orchestrate antifungal immunity. Nat Immunol 13(9):817–822

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Higuero AM, Díez-Revuelta N, Abad-Rodríguez J (2017) The sugar code in neuronal physiology. Histochem Cell Biol 147(2). doi:10.1007/s00418-016-1519-3

  • Hütter J, Eriksson M, Johannssen T, Klopfleisch R, von Smolinski D, Gruber AD, Seeberger PH, Lepenies B (2014) Role of the C-type lectin receptors MCL and DCIR in experimental colitis. PLoS ONE 9(7):e103281

    Article  PubMed  PubMed Central  Google Scholar 

  • Ifrim DC, Bain JM, Reid DM, Oosting M, Verschueren I, Gow NA, van Krieken JH, Brown GD, Kullberg BJ, Joosten LA, van der Meer JW, Koentgen F, Erwig LP, Quintin J, Netea MG (2014) Role of Dectin-2 for host defense against systemic infection with Candida glabrata. Infect Immun 82(3):1064–1073

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Iliev ID, Funari VA, Taylor KD, Nguyen Q, Reyes CN, Strom SP, Brown J, Becker CA, Fleshner PR, Dubinsky M, Rotter JI, Wang HL, McGovern DP, Brown GD, Underhill DM (2012) Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis. Science 336(6086):1314–1317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ishibashi S, Hammer RE, Herz J (1994) Asialoglycoprotein receptor deficiency in mice lacking the minor receptor subunit. J Biol Chem 269(45):27803–27806

    CAS  PubMed  Google Scholar 

  • Ishikawa E, Ishikawa T, Morita YS, Toyonaga K, Yamada H, Takeuchi O, Kinoshita T, Akira S, Yoshikai Y, Yamasaki S (2009) Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle. J Exp Med 206(13):2879–2888

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jaillon S, Ponzetta A, Magrini E, Barajon I, Barbagallo M, Garlanda C, Mantovani A (2016) Fluid phase recognition molecules in neutrophil-dependent immune responses. Semin Immunol 28(2):109–118

    Article  CAS  PubMed  Google Scholar 

  • Johannssen T, Lepenies B (2017) Glycan-based cell targeting to modulate immune responses. Trends Biotechnol. doi:10.1016/j.tibtech.2016.10.002

    Google Scholar 

  • Kaltner H, Toegel S, Garcia Caballero G, Manning JC, Ledeen RW, Gabius H-J (2017) Galectins: their network and roles in immunity/tumor growth control. Histochem Cell Biol 147(2). doi:10.1007/s00418-016-1522-8

  • Kanazawa N (2007) Dendritic cell immunoreceptors: C-type lectin receptors for pattern-recognition and signaling on antigen-presenting cells. J Dermatol Sci 45(2):77–86

    Article  CAS  PubMed  Google Scholar 

  • Kerrigan AM, Brown GD (2011) Syk-coupled C-type lectins in immunity. Trends Immunol 32(4):151–156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kerscher B, Willment JA, Brown GD (2013) The Dectin-2 family of C-type lectin-like receptors: an update. Int Immunol 25(5):271–277

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kikkeri R, Lepenies B, Adibekian A, Laurino P, Seeberger PH (2009) In vitro imaging and in vivo liver targeting with carbohydrate capped quantum dots. J Am Chem Soc 131(6):2110–2112

    Article  CAS  PubMed  Google Scholar 

  • Kingeter LM, Lin X (2012) C-type lectin receptor-induced NF-kappaB activation in innate immune and inflammatory responses. Cell Mol Immunol 9(2):105–112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klaver EJ, Kuijk LM, Laan LC, Kringel H, van Vliet SJ, Bouma G, Cummings RD, Kraal G, van Die I (2013) Trichuris suis-induced modulation of human dendritic cell function is glycan-mediated. Int J Parasitol 43(3–4):191–200

    Article  CAS  PubMed  Google Scholar 

  • Kopitz J (2017) Lipid glycosylation: a primer for histochemists and cell biologists. Histochem Cell Biol 147(2). doi:10.1007/s00418-016-1518-4

  • Kumagai Y, Akira S (2010) Identification and functions of pattern-recognition receptors. J Allergy Clin Immunol 125(5):985–992

    Article  CAS  PubMed  Google Scholar 

  • Lee SJ, Evers S, Roeder D, Parlow AF, Risteli J, Risteli L, Lee YC, Feizi T, Langen H, Nussenzweig MC (2002) Mannose receptor-mediated regulation of serum glycoprotein homeostasis. Science 295(5561):1898–1901

    Article  CAS  PubMed  Google Scholar 

  • Lepenies B, Lee J, Sonkaria S (2013) Targeting C-type lectin receptors with multivalent carbohydrate ligands. Adv Drug Deliv Rev 65(9):1271–1281

    Article  CAS  PubMed  Google Scholar 

  • Lightfoot YL, Selle K, Yang T, Goh YJ, Sahay B, Zadeh M, Owen JL, Colliou N, Li E, Johannssen T, Lepenies B, Klaenhammer TR, Mohamadzadeh M (2015) SIGNR3-dependent immune regulation by Lactobacillus acidophilus surface layer protein A in colitis. EMBO J 34(7):881–895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lobato-Pascual A, Saether PC, Fossum S, Dissen E, Daws MR (2013) Mincle, the receptor for mycobacterial cord factor, forms a functional receptor complex with MCL and FcepsilonRI-gamma. Eur J Immunol 43(12):3167–3174

    Article  CAS  PubMed  Google Scholar 

  • Lozach PY, Burleigh L, Staropoli I, Amara A (2007) The C type lectins DC-SIGN and L-SIGN: receptors for viral glycoproteins. Methods Mol Biol 379:51–68

    Article  CAS  PubMed  Google Scholar 

  • Lugo-Villarino G, Hudrisier D, Tanne A, Neyrolles O (2011) C-type lectins with a sweet spot for Mycobacterium tuberculosis. Eur J Microbiol Immunol (Bp) 1(1):25–40

    Article  CAS  Google Scholar 

  • Maeda N, Nigou J, Herrmann JL, Jackson M, Amara A, Lagrange PH, Puzo G, Gicquel B, Neyrolles O (2003) The cell surface receptor DC-SIGN discriminates between Mycobacterium species through selective recognition of the mannose caps on lipoarabinomannan. J Biol Chem 278(8):5513–5516

    Article  CAS  PubMed  Google Scholar 

  • Maglinao M, Klopfleisch R, Seeberger PH, Lepenies B (2013) The C-type lectin receptor DCIR is crucial for the development of experimental cerebral malaria. J Immunol 191(5):2551–2559

    Article  CAS  PubMed  Google Scholar 

  • Maglinao M, Eriksson M, Schlegel MK, Zimmermann S, Johannssen T, Götze S, Seeberger PH, Lepenies B (2014) A platform to screen for C-type lectin receptor-binding carbohydrates and their potential for cell-specific targeting and immune modulation. J Control Release 175:36–42

    Article  CAS  PubMed  Google Scholar 

  • Manning JC, Romero A, Habermann F, Garcia Caballero G, Kaltner H, Roth J, Gabius H-J (2017) Lectins: a primer for histochemists and cell biologists. Histochem Cell Biol 147(2). doi:10.1007/s00418-016-1524-6

  • Marshall AS, Willment JA, Lin HH, Williams DL, Gordon S, Brown GD (2004) Identification and characterization of a novel human myeloid inhibitory C-type lectin-like receptor (MICL) that is predominantly expressed on granulocytes and monocytes. J Biol Chem 279(15):14792–14802

    Article  CAS  PubMed  Google Scholar 

  • Martínez-Ávila O, Hijazi K, Marradi M, Clavel C, Campion C, Kelly C, Penadés S (2009) Gold manno-glyconanoparticles: multivalent systems to block HIV-1 gp120 binding to the lectin DC-SIGN. Chem Eur J 15(38):9874–9888

    Article  PubMed  CAS  Google Scholar 

  • 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(5623):1295–1297

    Article  CAS  PubMed  Google Scholar 

  • McEver RP (2015) Selectins: initiators of leukocyte adhesion and signaling at the vascular wall. Cardiovasc Res 107(3):331–339

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mickum ML, Rojsajjakul T, Yu Y, Cummings RD (2016) Schistosoma mansoni alpha1,3-fucosyltransferase-F generates the Lewis X antigen. Glycobiology 26(3):270–285

    CAS  PubMed  Google Scholar 

  • Mitchell DE, Gibson MI (2015) Latent ice recrystallization inhibition activity in nonantifreeze proteins: Ca2+-activated plant lectins and cation-activated antimicrobial peptides. Biomacromolecules 16(10):3411–3416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miyake Y, Ishikawa E, Ishikawa T, Yamasaki S (2010) Self and nonself recognition through C-type lectin receptor, Mincle. Self Nonself 1(4):310–313

    Article  PubMed  PubMed Central  Google Scholar 

  • Müller U, Vogel P, Alber G, Schaub GA (2008) The innate immune system of mammals and insects. Contrib Microbiol 15:21–44

    PubMed  Google Scholar 

  • Neumann K, Castineiras-Vilarino M, Höckendorf U, Hannesschläger N, Lemeer S, Kupka D, Meyermann S, Lech M, Anders HJ, Kuster B, Busch DH, Gewies A, Naumann R, Groß O, Ruland J (2014) Clec12a is an inhibitory receptor for uric acid crystals that regulates inflammation in response to cell death. Immunity 40(3):389–399

    Article  CAS  PubMed  Google Scholar 

  • Osorio F, Reis e Sousa C (2011) Myeloid C-type lectin receptors in pathogen recognition and host defense. Immunity 34(5):651–664

    Article  CAS  PubMed  Google Scholar 

  • Pees B, Yang W, Zarate-Potes A, Schulenburg H, Dierking K (2016) High innate immune specificity through diversified C-type lectin-like domain proteins in invertebrates. J Innate Immun 8(2):129–142

    Article  CAS  PubMed  Google Scholar 

  • Pegram HJ, Andrews DM, Smyth MJ, Darcy PK, Kershaw MH (2011) Activating and inhibitory receptors of natural killer cells. Immunol Cell Biol 89(2):216–224

    Article  PubMed  Google Scholar 

  • Plato A, Willment JA, Brown GD (2013) C-type lectin-like receptors of the dectin-1 cluster: ligands and signaling pathways. Int Rev Immunol 32(2):134–156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rabes A, Zimmermann S, Reppe K, Lang R, Seeberger PH, Suttorp N, Witzenrath M, Lepenies B, Opitz B (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(2):e0117022

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ribeiro-Viana R, Sanchez-Navarro M, Luczkowiak J, Koeppe JR, Delgado R, Rojo J, Davis BG (2012) Virus-like glycodendrinanoparticles displaying quasi-equivalent nested polyvalency upon glycoprotein platforms potently block viral infection. Nat Commun 3:1303

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Richardson MB, Williams SJ (2014) MCL and Mincle: C-type lectin receptors that sense damaged self and pathogen-associated molecular patterns. Front Immunol 5:288

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ritter M, Gross O, Kays S, Ruland J, Nimmerjahn F, Saijo S, Tschopp J, Layland LE, Prazeres da Costa C (2010) Schistosoma mansoni triggers Dectin-2, which activates the Nlrp3 inflammasome and alters adaptive immune responses. Proc Natl Acad Sci USA 107(47):20459–20464

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Robinson MJ, Sancho D, Slack EC, LeibundGut-Landmann S, Reis e Sousa C (2006) Myeloid C-type lectins in innate immunity. Nat Immunol 7(12):1258–1265

    Article  CAS  PubMed  Google Scholar 

  • Robinson MJ, Osorio F, Rosas M, Freitas RP, Schweighoffer E, Groß O, Verbeek JS, Ruland J, Tybulewicz V, Brown GD, Moita LF, Taylor PR, Reis e Sousa C (2009) Dectin-2 is a Syk-coupled pattern recognition receptor crucial for Th17 responses to fungal infection. J Exp Med 206(9):2037–2051

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rogers JC, Kornfeld S (1971) Hepatic uptake of proteins coupled to fetuin glycopeptide. Biochem Biophys Res Commun 45(3):622–629

    Article  CAS  PubMed  Google Scholar 

  • Roth J (2011) Lectins for histochemical demonstration of glycans. Histochem Cell Biol 136(2):117–130

    Article  CAS  PubMed  Google Scholar 

  • Roy R, Cao Y, Kaltner H, Kottari N, Shiao TC, Belkhadem K, André S, Manning JC, Murphy PV, Gabius H-J (2017) Teaming up synthetic chemistry and histochemistry for activity screening in galectin-directed inhibitor design. Histochem Cell Biol 147(2). doi:10.1007/s00418-016-1525-5

  • Saba K, Denda-Nagai K, Irimura T (2009) A C-type lectin MGL1/CD301a plays an anti-inflammatory role in murine experimental colitis. Am J Pathol 174(1):144–152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saijo S, Fujikado N, Furuta T, Chung SH, Kotaki H, Seki K, Sudo K, Akira S, Adachi Y, Ohno N, Kinjo T, Nakamura K, Kawakami K, Iwakura Y (2007) Dectin-1 is required for host defense against Pneumocystis carinii but not against Candida albicans. Nat Immunol 8(1):39–46

    Article  CAS  PubMed  Google Scholar 

  • Saijo S, Ikeda S, Yamabe K, Kakuta S, Ishigame H, Akitsu A, Fujikado N, Kusaka T, Kubo S, Chung SH, Komatsu R, Miura N, Adachi Y, Ohno N, Shibuya K, Yamamoto N, Kawakami K, Yamasaki S, Saito T, Akira S, Iwakura Y (2010) Dectin-2 recognition of α-mannans and induction of Th17 cell differentiation is essential for host defense against Candida albicans. Immunity 32(5):681–691

    Article  CAS  PubMed  Google Scholar 

  • Saunders SP, Barlow JL, Walsh CM, Bellsoi A, Smith P, McKenzie AN, Fallon PG (2010) C-type lectin SIGN-R1 has a role in experimental colitis and responsiveness to lipopolysaccharide. J Immunol 184(5):2627–2637

    Article  CAS  PubMed  Google Scholar 

  • Schoenen H, Bodendorfer B, Hitchens K, Manzanero S, Werninghaus K, Nimmerjahn F, Agger EM, Stenger S, Andersen P, Ruland J, Brown GD, Wells C, Lang R (2010) Cutting edge: Mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analog trehalose-dibehenate. J Immunol 184(6):2756–2760

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sharma A, Steichen AL, Jondle CN, Mishra BB, Sharma J (2014) Protective role of Mincle in bacterial pneumonia by regulation of neutrophil mediated phagocytosis and extracellular trap formation. J Infect Dis 209(11):1837–1846

    Article  CAS  PubMed  Google Scholar 

  • Solis D, Bovin NV, Davis AP, Jimenez-Barbero J, Romero A, Roy R, Smetana K Jr, Gabius HJ (2015) A guide into glycosciences: how chemistry, biochemistry and biology cooperate to crack the sugar code. Biochim Biophys Acta 1850(1):186–235

    Article  CAS  PubMed  Google Scholar 

  • Švajger U, Anderluh M, Jeras M, Obermajer N (2010) C-type lectin DC-SIGN: an adhesion, signalling and antigen-uptake molecule that guides dendritic cells in immunity. Cell Signal 22(10):1397–1405

    Article  PubMed  CAS  Google Scholar 

  • Tailleux L, Schwartz O, Herrmann J-L, Pivert E, Jackson M, Amara A, Legres L, Dreher D, Nicod LP, Gluckman JC, Lagrange PH, Gicquel B, Neyrolles O (2003) DC-SIGN is the major Mycobacterium tuberculosis receptor on human dendritic cells. J Exp Med 197(1):121–127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takeuchi O, Akira S (2010) Pattern recognition receptors and inflammation. Cell 140(6):805–820

    Article  CAS  PubMed  Google Scholar 

  • Taylor PR, Brown GD, Herre J, Williams DL, Willment JA, Gordon S (2004) The role of SIGNR1 and the beta-glucan receptor (dectin-1) in the nonopsonic recognition of yeast by specific macrophages. J Immunol 172(2):1157–1162

    Article  CAS  PubMed  Google Scholar 

  • Taylor PR, Reid DM, Heinsbroek SE, Brown GD, Gordon S, Wong SY (2005) Dectin-2 is predominantly myeloid restricted and exhibits unique activation-dependent expression on maturing inflammatory monocytes elicited in vivo. Eur J Immunol 35(7):2163–2174

    Article  CAS  PubMed  Google Scholar 

  • Taylor PR, Tsoni SV, Willment JA, Dennehy KM, Rosas M, Findon H, Haynes K, Steele C, Botto M, Gordon S, Brown GD (2007) Dectin-1 is required for beta-glucan recognition and control of fungal infection. Nat Immunol 8(1):31–38

    Article  CAS  PubMed  Google Scholar 

  • Tokieda S, Komori M, Ishiguro T, Iwakura Y, Takahara K, Inaba K (2015) Dendritic cell immunoreceptor 1 alters neutrophil responses in the development of experimental colitis. BMC Immunol 16(1):64

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Underhill DM, Goodridge HS (2007) The many faces of ITAMs. Trends Immunol 28(2):66–73

    Article  CAS  PubMed  Google Scholar 

  • Unger WW, van Beelen AJ, Bruijns SC, Joshi M, Fehres CM, van Bloois L, Verstege MI, Ambrosini M, Kalay H, Nazmi K, Bolscher JG, Hooijberg E, de Gruijl TD, Storm G, van Kooyk Y (2012) Glycan-modified liposomes boost CD4+ and CD8+ T-cell responses by targeting DC-SIGN on dendritic cells. J Control Release 160(1):88–95

    Article  CAS  PubMed  Google Scholar 

  • van Kooyk Y, Geijtenbeek TB (2003) DC-SIGN: escape mechanism for pathogens. Nat Rev Immunol 3(9):697–709

    Article  PubMed  CAS  Google Scholar 

  • van Kooyk Y, Engering A, Lekkerkerker AN, Ludwig IS, Geijtenbeek TB (2004) Pathogens use carbohydrates to escape immunity induced by dendritic cells. Curr Opin Immunol 16(4):488–493

    Article  PubMed  CAS  Google Scholar 

  • van Kooyk Y, Unger WW, Fehres CM, Kalay H, García-Vallejo JJ (2013) Glycan-based DC-SIGN targeting vaccines to enhance antigen cross-presentation. Mol Immunol 55(2):143–145

    Article  PubMed  CAS  Google Scholar 

  • Vautier S, MacCallum DM, Brown GD (2012) C-type lectin receptors and cytokines in fungal immunity. Cytokine 58(1):89–99

    Article  CAS  PubMed  Google Scholar 

  • Vivier E, Nunès JA, Vély F (2004) Natural killer cell signaling pathways. Science 306(5701):1517–1519

    Article  CAS  PubMed  Google Scholar 

  • Wang S-K, Liang P-H, Astronomo RD, Hsu T-L, Hsieh S-L, Burton DR, Wong C-H (2008) Targeting the carbohydrates on HIV-1: interaction of oligomannose dendrons with human monoclonal antibody 2G12 and DC-SIGN. Proc Natl Acad Sci USA 105(10):3690–3695

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wells CA, Salvage-Jones JA, Li X, Hitchens K, Butcher S, Murray RZ, Beckhouse AG, Lo YL, Manzanero S, Cobbold C, Schroder K, Ma B, Orr S, Stewart L, Lebus D, Sobieszczuk P, Hume DA, Stow J, Blanchard H, Ashman RB (2008) The macrophage-inducible C-type lectin, Mincle, is an essential component of the innate immune response to Candida albicans. J Immunol 180(11):7404–7413

    Article  CAS  PubMed  Google Scholar 

  • Werninghaus K, Babiak A, Groß O, Hölscher C, Dietrich H, Agger EM, Mages J, Mocsai A, Schoenen H, Finger K, Nimmerjahn F, Brown GD, Kirschning C, Heit A, Andersen P, Wagner H, Ruland J, Lang R (2009) Adjuvanticity of a synthetic cord factor analogue for subunit Mycobacterium tuberculosis vaccination requires FcRγ–Syk–Card9–dependent innate immune activation. J Exp Med 206(1):89–97

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wittmann A, Lamprinaki D, Bowles KM, Katzenellenbogen E, Knirel YA, Whitfield C, Nishimura T, Matsumoto N, Yamamoto K, Iwakura Y, Saijo S, Kawasaki N (2016) Dectin-2 recognizes mannosylated O-antigens of human opportunistic pathogens and augments lipopolysaccharide activation of myeloid cells. J Biol Chem 291(34):17629–17638

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu B, Hur S (2015) How RIG-I like receptors activate MAVS. Curr Opin Virol 12:91–98

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yabe R, Iwakura Y, Saijo S (2014) The role of C-type lectin receptors in the host defense against microbial pathogens. In: Endo T, Seeberger HP, Hart WG, Wong C-H, Taniguchi N (eds) Glycoscience: Biology and Medicine. Springer Japan, Tokyo

    Google Scholar 

  • Yamasaki S, Ishikawa E, Sakuma M, Hara H, Ogata K, Saito T (2008) Mincle is an ITAM-coupled activating receptor that senses damaged cells. Nat Immunol 9(10):1179–1188

    Article  CAS  PubMed  Google Scholar 

  • Yamasaki S, Matsumoto M, Takeuchi O, Matsuzawa T, Ishikawa E, Sakuma M, Tateno H, Uno J, Hirabayashi J, Mikami Y, Takeda K, Akira S, Saito T (2009) C-type lectin Mincle is an activating receptor for pathogenic fungus, Malassezia. Proc Natl Acad Sci USA 106(6):1897–1902

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yonekawa A, Saijo S, Hoshino Y, Miyake Y, Ishikawa E, Suzukawa M, Inoue H, Tanaka M, Yoneyama M, Oh-Hora M, Akashi K, Yamasaki S (2014) Dectin-2 is a direct receptor for mannose-capped lipoarabinomannan of mycobacteria. Immunity 41(3):402–413

    Article  CAS  PubMed  Google Scholar 

  • Zarbock A, Ley K, McEver RP, Hidalgo A (2011) Leukocyte ligands for endothelial selectins: specialized glycoconjugates that mediate rolling and signaling under flow. Blood 118(26):6743–6751

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zelensky AN, Gready JE (2005) The C-type lectin-like domain superfamily. FEBS J 272(24):6179–6217

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Funding by the Niedersachsen-Research Network on Neuroinfectiology (N-RENNT) is gratefully acknowledged.

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Correspondence to Bernd Lepenies.

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Sabine Mayer and Marie-Kristin Raulf have contributed equally to this manuscript.

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Mayer, S., Raulf, MK. & Lepenies, B. C-type lectins: their network and roles in pathogen recognition and immunity. Histochem Cell Biol 147, 223–237 (2017). https://doi.org/10.1007/s00418-016-1523-7

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