From structure to function - Ligand recognition by myeloid C-type lectin receptors

Abstract

The relevance of protein-glycan interactions in immunity has long been underestimated. Yet, the immune system possesses numerous classes of glycan-binding proteins, so-called lectins. Of specific interest is the group of myeloid C-type lectin receptors (CLRs) as they are mainly expressed by myeloid cells and play an important role in the initiation of an immune response. Myeloid CLRs represent a major group amongst pattern recognition receptors (PRRs), placing them at the center of the rapidly growing field of glycoimmunology. CLRs have evolved to encompass a wide range of structures and functions and to recognize a large number of glycans and many other ligands from different classes of biopolymers. This review aims at providing the reader with an overview of myeloid CLRs and selected ligands, while highlighting recent insights into CLR-ligand interactions. Subsequently, methodological approaches in CLR-ligand research will be presented. Finally, this review will discuss how CLR-ligand interactions culminate in immunological functions, how glycan mimicry favors immune escape by pathogens, and in which way immune responses can be affected by CLR-ligand interactions in the long term.

Keywords: BCG, Bacillus Calmette-Guérin; C-type lectin receptors; CLR, C-type lectin receptor; CRD, Carbohydrate recognition domain; CTL, C-type lectin; CTLD, C-type lectin-like domain; DAMP, Danger-associated molecular pattern; DAP12, DNAX-activation protein 12; DC, Dendritic cell; DC-SIGN, Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin; DCAR, Dendritic cell immunoactivating receptor; DCIR, Dendritic cell immunoreceptor; DLS, Dynamic light scattering; DNGR, Dendritic cell natural killer lectin group receptor; Dectin, Dendritic cell-associated C-type lectin receptor; ECD, Extracellular domain; ECM, Experimental cerebral malaria; ELISA, Enzyme-linked-immunosorbent-assay; FRET, Förster resonance energy transfer; Fc, Fragment crystallizable; FcRγ, Fragment crystallizable receptor γ; Fuc, Fucose; GTfs, Glycosyltransferases; Gal, Galactose; GalNAc, N-acetylgalactosamine; Glc, Glucose; GlcNAc, N-acetylglucosamine; HIV-1, Human immunodeficiency virus 1; HLA, Human leukocyte antigen; HSPC, Hematopoietic stem and progenitor cells; Host-pathogen interaction; IL, Interleukin; ITAM, Immunoreceptor tyrosine-based activating motif; ITC, Isothermal titration calorimetry; ITIM, Immunoreceptor tyrosine-based inhibitory motif; Ig, Immunoglobulin; Immune modulation; LPS, Lipopolysaccharide; Lac, Lactose (Gal-β1,4-Glc); LacNAc, N-acetyllactosamine (Gal-β1,4-GlcNAc); Le, Lewis; Ligand identification; MBP, Mannan-binding protein; MCL, Macrophage C-type lectin; MD, Molecular dynamics; MDL, Myeloid DAP12-associating lectin; MGDG, Monoglucosyldiacylglycerol; MGL, Macrophage galactose-type lectin; MHC, Major histocompatibility complex; MICL, Myeloid inhibitory C type-like lectin; MMR, Macrophage mannose receptor; MSU, Monosodium urate; Man, Mannose; Mincle, Macrophage inducible Ca2+-dependent lectin receptor; Mφ, Macrophages; NF-κB, Nuclear factor kappa B; NFAT, Nuclear factor of activated T-cells; NK, Natural killer (cells); NMR, Nuclear magnet resonance; PAMP, Pathogen-associated molecular pattern; PDPN, Podoplanin; PRR, Pattern recognition receptor; QCM, Quartz crystal microbalance; RIA, Radioimmunoassays; ROS, Reactive oxygen species; Raf-1, Rapidly accelerated fibrosarcoma 1; SAMP, Self-associated molecular pattern; SAP130, Spliceosome-associated protein 130; SARS-CoV, SARS coronavirus; SH2, Src-homology 2; SHP, Src homology region 2 domain-containing phosphatase; SIGNR, Specific intracellular adhesion molecule-3 grabbing non-integrin homolog-related; SPR, Surface plasmon resonance; SYK, Spleen tyrosine kinase; Self-non-self-discrimination; Signaling flexibility; TCA, Tricarboxylic acid; TDM, Trehalose-6,6′-dimycolate; TLC, Thin-layer chromatography; TLR, Toll-like receptor; TNF, Tumor necrosis factor; WTA, Wall teichoic acid; mTOR, Mammalian target of rapamycin.