Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Journal of Laboratory Medicine

Official Journal of the German Society of Clinical Chemistry and Laboratory Medicine

Editor-in-Chief: Schuff-Werner, Peter

Ed. by Ahmad-Nejad, Parviz / Bidlingmaier, Martin / Bietenbeck, Andreas / Conrad, Karsten / Findeisen, Peter / Fraunberger, Peter / Ghebremedhin, Beniam / Holdenrieder, Stefan / Kiehntopf, Michael / Klein, Hanns-Georg / Kohse, Klaus P. / Kratzsch, Jürgen / Luppa, Peter B. / Meyer, Alexander von / Nebe, Carl Thomas / Orth, Matthias / Röhrig-Herzog, Gabriele / Sack, Ulrich / Steimer, Werner / Weber, Thomas / Wieland, Eberhard / Winter, Christof / Zettl, Uwe K.


IMPACT FACTOR 2018: 0.389

CiteScore 2018: 0.22

SCImago Journal Rank (SJR) 2018: 0.156
Source Normalized Impact per Paper (SNIP) 2018: 0.089

Online
ISSN
2567-9449
See all formats and pricing
More options …
Volume 38, Issue 6

Issues

Immune sensing by activating and inhibitory C-type lectin receptors

Immunerkennung durch aktivierende und hemmende C-Typ-Lektin-Rezeptoren

Konstantin Neumann
  • Corresponding author
  • Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Jürgen Ruland
  • Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2014-12-02 | DOI: https://doi.org/10.1515/labmed-2014-0044

Abstract

The innate immune system uses a defined set of germ-line-encoded pattern recognition receptors (PRRs) to recognize microbes or non-microbial forms of danger and subsequently activates an inflammatory response. In the last decade, several myeloid PRRs have been identified that utilize intracellular signaling modules called immunoreceptor tyrosine-based activation motifs (ITAMs). These ITAM-coupled C-type lectin domain-containing receptors (CLRs) recognize both pathogen-associated pattern (PAMPs) and host-derived danger molecules. To balance immunity, these CLRs can be counteracted by inhibitory receptors harboring an immunoreceptor tyrosine-based inhibitory motif (ITIM). This mini-review summarizes the current knowledge of the function and regulation of ITAM- and ITIM-coupled CLRs and their relevance in immune homeostasis and host defense.

Zusammenfassung

Das angeborene Immunsystem verwendet einen definierten Satz von keimbahn-kodierten Mustererkennungsrezeptoren (pattern recognition Rezeptoren [PRR]), um Mikroben oder nicht-mikrobielle Gefahrensignale zu erkennen und eine entzündliche Reaktion zu aktivieren. In den letzten zehn Jahren sind mehrere myeloische PRRs identifiziert worden, die intrazelluläre Immunrezeptor Tyrosin-basierte Aktivierungsmotive (ITAMs) zur Signalübertragung nutzen. Diese ITAM-gekoppelten C-Typ Lektin Rezeptoren (CLRs) erkennen sowohl Pathogen-assoziierte Muster als auch wirtseigene Moleküle, welche Gefahr oder Stress anzeigen. Um die Immunantwort auszubalancieren werden diese CLRs durch inhibitorische Rezeptoren gehemmt, die ein Immunrezeptor Tyrosin-basiertes Inhibitionsmotiv (ITIM) enthalten. Dieser Review fasst das aktuelle Wissen über die Funktion und Regulation von ITAM- und ITIM- gekoppelten CLRs und ihre Relevanz in Immunhomöostase und -abwehr zusammen.

Keywords: C-type lectin receptors; damage-associated molecular patterns; immunoreceptor tyrosine-based activation motif (ITAM); immunoreceptor tyrosine-based inhibitory motif (ITIM); inflammation; pattern recognition receptors; uric acid crystals

Schlüsselwörter:: C-Typ Lektin-Rezeptoren; Harnsäure-Kristalle; ITAM; ITIM; Immunrezeptoren; Zelltod-induzierte Entzündung

References

  • 1.

    Janeway CA, Jr. Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harbor symposia on quantitative biology. 1989;54 Pt 1:1–13.Google Scholar

  • 2.

    Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell 2010;140:805–20.Web of ScienceGoogle Scholar

  • 3.

    Palm NW, Medzhitov R. Pattern recognition receptors and control of adaptive immunity. Immunological reviews. 2009;227:221–33.Web of ScienceGoogle Scholar

  • 4.

    Kaczmarek A, Vandenabeele P, Krysko DV. Necroptosis: the release of damage-associated molecular patterns and its physiological relevance. Immunity 2013;38:209–23.CrossrefWeb of SciencePubMedGoogle Scholar

  • 5.

    Kroemer G, Galluzzi L, Kepp O, Zitvogel L. Immunogenic cell death in cancer therapy. Annu Rev Immunol 2013;31:51–72.PubMedCrossrefGoogle Scholar

  • 6.

    Jiang D, Liang J, Fan J, Yu S, Chen S, Luo Y, et al. Regulation of lung injury and repair by Toll-like receptors and hyaluronan. Nat Med 2005;11:1173–9.CrossrefPubMedGoogle Scholar

  • 7.

    Imaeda AB, Watanabe A, Sohail MA, Mahmood S, Mohamadnejad M, Sutterwala FS, et al. Acetaminophen-induced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3 inflammasome. The Journal of clinical investigation. 2009;119:305–14.Google Scholar

  • 8.

    Arslan F, Smeets MB, O’Neill LA, Keogh B, McGuirk P, Timmers L, et al. Myocardial ischemia/reperfusion injury is mediated by leukocytic toll-like receptor-2 and reduced by systemic administration of a novel anti-toll-like receptor-2 antibody. Circulation 2010;121:80–90.CrossrefGoogle Scholar

  • 9.

    Iborra S, Sancho D. Signalling versatility following self and non-self sensing by myeloid C-type lectin receptors. Immunobiology 2014 (in press). PubMed PMID: 25269828.Web of ScienceGoogle Scholar

  • 10.

    Kerscher B, Willment JA, Brown GD. The Dectin-2 family of C-type lectin-like receptors: an update. Int Immunol 2013;25:271–7.CrossrefWeb of ScienceGoogle Scholar

  • 11.

    Plato A, Willment JA, Brown GD. C-type lectin-like receptors of the dectin-1 cluster: ligands and signaling pathways. Int Rev Immunol 2013;32:134–56.PubMedGoogle Scholar

  • 12.

    Reth M. Antigen receptor tail clue. Nature 1989;338:383–4.Google Scholar

  • 13.

    Rogers NC, Slack EC, Edwards AD, Nolte MA, Schulz O, Schweighoffer E, et al. Syk-dependent cytokine induction by Dectin-1 reveals a novel pattern recognition pathway for C type lectins. Immunity 2005;22:507–17.PubMedGoogle Scholar

  • 14.

    Goodridge HS, Reyes CN, Becker CA, Katsumoto TR, Ma J, Wolf AJ, et al. Activation of the innate immune receptor Dectin-1 upon formation of a ‘phagocytic synapse’. Nature 2011;472:471–5.Web of SciencePubMedGoogle Scholar

  • 15.

    Brown GD, Gordon S. Immune recognition. A new receptor for beta-glucans. Nature 2001;413:36–7.Google Scholar

  • 16.

    Chiba S, Ikushima H, Ueki H, Yanai H, Kimura Y, Hangai S, et al. Recognition of tumor cells by Dectin-1 orchestrates innate immune cells for anti-tumor responses. eLife 2014;3:e04177.Web of ScienceGoogle Scholar

  • 17.

    Ishikawa E, Ishikawa T, Morita YS, Toyonaga K, Yamada H, Takeuchi O, et al. Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle. J Exp Med 2009;206:2879–88.Web of ScienceGoogle Scholar

  • 18.

    Schoenen H, Bodendorfer B, Hitchens K, Manzanero S, Werninghaus K, Nimmerjahn F, et al. Cutting edge: mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analog trehalose-dibehenate. J Immunol 2010;184:2756–60.Web of ScienceGoogle Scholar

  • 19.

    Yamasaki S, Ishikawa E, Sakuma M, Hara H, Ogata K, Saito T. Mincle is an ITAM-coupled activating receptor that senses damaged cells. Nat Immunol 2008;9:1179–88.PubMedCrossrefGoogle Scholar

  • 20.

    Yamasaki S, Matsumoto M, Takeuchi O, Matsuzawa T, Ishikawa E, Sakuma M, et al. C-type lectin Mincle is an activating receptor for pathogenic fungus, Malassezia. Proc Natl Acad Sci USA 2009;106:1897–902.CrossrefGoogle Scholar

  • 21.

    Mocsai A, Ruland J, Tybulewicz VL. The SYK tyrosine kinase: a crucial player in diverse biological functions. Nat Rev Immunol 2010;10:387–402.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 22.

    Wienands J, Schweikert J, Wollscheid B, Jumaa H, Nielsen PJ, Reth M. SLP-65: a new signaling component in B lymphocytes which requires expression of the antigen receptor for phosphorylation. J Exp Med 1998;188:791–5.Google Scholar

  • 23.

    Chiu CW, Dalton M, Ishiai M, Kurosaki T, Chan AC. BLNK: molecular scaffolding through ‘cis’-mediated organization of signaling proteins. EMBO J 2002;21:6461–72.CrossrefPubMedGoogle Scholar

  • 24.

    Sommer K, Guo B, Pomerantz JL, Bandaranayake AD, Moreno-Garcia ME, Ovechkina YL, et al. Phosphorylation of the CARMA1 linker controls NF-kappaB activation. Immunity 2005;23:561–74.CrossrefGoogle Scholar

  • 25.

    Gross O, Gewies A, Finger K, Schafer M, Sparwasser T, Peschel C, et al. Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity. Nature 2006;442:651–6.Google Scholar

  • 26.

    Tassi I, Cella M, Castro I, Gilfillan S, Khan WN, Colonna M. Requirement of phospholipase C-gamma2 (PLCgamma2) for Dectin-1-induced antigen presentation and induction of TH1/TH17 polarization. Eur J Immunol 2009;39:1369–78.Web of ScienceGoogle Scholar

  • 27.

    Strasser D, Neumann K, Bergmann H, Marakalala MJ, Guler R, Rojowska A, et al. Syk kinase-coupled C-type lectin receptors engage protein kinase C-sigma to elicit Card9 adaptor-mediated innate immunity. Immunity 2012;36:32–42.CrossrefPubMedGoogle Scholar

  • 28.

    Gringhuis SI, den Dunnen J, Litjens M, van der Vlist M, Wevers B, Bruijns SC, et al. Dectin-1 directs T helper cell differentiation by controlling noncanonical NF-kappaB activation through Raf-1 and Syk. Nat Immunol 2009;10:203–13.Web of ScienceGoogle Scholar

  • 29.

    Orr SJ, Burg AR, Chan T, Quigley L, Jones GW, Ford JW, et al. LAB/NTAL facilitates fungal/PAMP-induced IL-12 and IFN-gamma production by repressing beta-catenin activation in dendritic cells. PLoS Pathogens 2013;9:e1003357.CrossrefWeb of ScienceGoogle Scholar

  • 30.

    Wevers BA, Kaptein TM, Zijlstra-Willems EM, Theelen B, Boekhout T, Geijtenbeek TB, et al. Fungal engagement of the C-type lectin mincle suppresses dectin-1-induced antifungal immunity. Cell Host & Microbe 2014;15:494–505.Web of SciencePubMedGoogle Scholar

  • 31.

    Sancho D, Joffre OP, Keller AM, Rogers NC, Martinez D, Hernanz-Falcon P, et al. Identification of a dendritic cell receptor that couples sensing of necrosis to immunity. Nature 2009;458:899–903.Web of ScienceGoogle Scholar

  • 32.

    Zelenay S, Keller AM, Whitney PG, Schraml BU, Deddouche S, Rogers NC, et al. The dendritic cell receptor DNGR-1 controls endocytic handling of necrotic cell antigens to favor cross- priming of CTLs in virus-infected mice. J Clin Invest 2012;122:1615–27.PubMedWeb of ScienceGoogle Scholar

  • 33.

    Ono M, Bolland S, Tempst P, Ravetch JV. Role of the inositol phosphatase SHIP in negative regulation of the immune system by the receptor Fc(gamma)RIIB. Nature 1996;383: 263–6.Google Scholar

  • 34.

    Neumann K, Oellerich T, Heine I, Urlaub H, Engelke M. Fc gamma receptor IIb modulates the molecular Grb2 interaction network in activated B cells. Cell Signal 2011;23:893–900.Web of ScienceCrossrefGoogle Scholar

  • 35.

    Nimmerjahn F, Ravetch JV. Fcgamma receptors as regulators of immune responses. Nat Rev Immunol 2008;8:34–47.PubMedCrossrefGoogle Scholar

  • 36.

    Smith KG, Clatworthy MR. FcgammaRIIB in autoimmunity and infection: evolutionary and therapeutic implications. Nat Rev Immunol 2010;10:328–43.Web of ScienceCrossrefPubMedGoogle Scholar

  • 37.

    Lanier LL. NK cell recognition. Ann Rev Immunol 2005;23: 225–74.CrossrefGoogle Scholar

  • 38.

    Fujikado N, Saijo S, Yonezawa T, Shimamori K, Ishii A, Sugai S, et al. Dcir deficiency causes development of autoimmune diseases in mice due to excess expansion of dendritic cells. Nat Med 2008;14:176–80.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 39.

    Maglinao M, Klopfleisch R, Seeberger PH, Lepenies B. The C-type lectin receptor DCIR is crucial for the development of experimental cerebral malaria. J Immunol 2013;191: 2551–9.Google Scholar

  • 40.

    Bloem K, Vuist IM, van den Berk M, Klaver EJ, van Die I, Knippels LM, et al. DCIR interacts with ligands from both endogenous and pathogenic origin. Immunol Lett 2014;158: 33–41.Web of ScienceGoogle Scholar

  • 41.

    Pyz E, Huysamen C, Marshall AS, Gordon S, Taylor PR, Brown GD. Characterisation of murine MICL (CLEC12A) and evidence for an endogenous ligand. Eur J Immunol 2008;38:1157–63.Web of ScienceCrossrefGoogle Scholar

  • 42.

    Neumann K, Castineiras-Vilarino M, Hockendorf U, Hannesschlager N, Lemeer S, Kupka D, et al. Clec12a is an inhibitory receptor for uric acid crystals that regulates inflammation in response to cell death. Immunity 2014;40:389–99.CrossrefWeb of ScienceGoogle Scholar

  • 43.

    Kono H, Chen CJ, Ontiveros F, Rock KL. Uric acid promotes an acute inflammatory response to sterile cell death in mice. J Clin Invest 2010;120:1939–49.Web of ScienceCrossrefPubMedGoogle Scholar

  • 44.

    Shi Y, Evans JE, Rock KL. Molecular identification of a danger signal that alerts the immune system to dying cells. Nature 2003;425:516–21.Google Scholar

  • 45.

    Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 2006;440:237–41.Google Scholar

  • 46.

    Ng G, Sharma K, Ward SM, Desrosiers MD, Stephens LA, Schoel WM, et al. Receptor-independent, direct membrane binding leads to cell-surface lipid sorting and Syk kinase activation in dendritic cells. Immunity 2008;29:807–18.PubMedCrossrefGoogle Scholar

  • 47.

    Barabe F, Gilbert C, Liao N, Bourgoin SG, Naccache PH. Crystal-induced neutrophil activation VI. Involvment of FcgammaRIIIB (CD16) and CD11b in response to inflammatory microcrystals. Faseb J 1998;12:209–20.Google Scholar

  • 48.

    Gagne V, Marois L, Levesque JM, Galarneau H, Lahoud MH, Caminschi I, et al. Modulation of monosodium urate crystal-induced responses in neutrophils by the myeloid inhibitory C-type lectin-like receptor: potential therapeutic implications. Arthritis Res Ther 2013;15:R73.Web of ScienceCrossrefPubMedGoogle Scholar

  • 49.

    Schwartz RH. Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy. Cell 1992;71:1065–8.Google Scholar

  • 50.

    Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012;12:252–64.PubMedCrossrefWeb of ScienceGoogle Scholar

About the article

Correspondence: Konstantin Neumann, Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany, E-Mail:


Received: 2014-11-06

Accepted: 2014-11-13

Published Online: 2014-12-02

Published in Print: 2014-12-01


Citation Information: LaboratoriumsMedizin, Volume 38, Issue 6, Pages 291–297, ISSN (Online) 1439-0477, ISSN (Print) 0342-3026, DOI: https://doi.org/10.1515/labmed-2014-0044.

Export Citation

©2014 by De Gruyter.Get Permission

Comments (0)

Please log in or register to comment.
Log in