Immune Recognition of Pathogen-Derived Glycolipids Through Mincle

  • Yasunobu MiyakeEmail author
  • Sho Yamasaki
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1204)


Mincle (macrophage inducible C-type lectin, Clec4e, Clecsf9) was originally identified as a member of the C-type lectin receptor family in 1999. Then, the function of Mincle to control antifungal immunity by binding to Candida albicans was reported in 2008. Around the same time, it was reported that Mincle recognized damaged cells and induced sterile inflammation by coupling with the ITAM-adaptor molecule FcRγ. In the following year, a breakthrough discovery reported that Mincle was an essential receptor for mycobacterial cord factor (trehalose-6,6′-dimycolate, TDM). Mincle gained increasing attention immediately after this critical finding. Although our understanding of the recognition of Mycobacteria has been advanced significantly, it was also revealed that Mincle interacts with pathogens other than Mycobacteria. In addition, endogenous ligands of Mincle were identified recently. Therefore, Mincle is now considered a danger receptor both for self and non-self ligands, so-called damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs). This chapter will give an overview of the accumulated knowledge of the multi-task danger receptor Mincle from its discovery to the latest findings.


C-type lectin receptor Danger signal Glycolipids 


  1. Agger EM et al (2008) Cationic liposomes formulated with synthetic mycobacterial cordfactor (CAF01): a versatile adjuvant for vaccines with different immunological requirements. PLoS ONE 3:e3116Google Scholar
  2. Andersen CS et al (2009) A simple mycobacterial monomycolated glycerol lipid has potent immunostimulatory activity. J Immunol 182:424–432CrossRefPubMedPubMedCentralGoogle Scholar
  3. Arce I et al (2004) The human C-type lectin CLECSF8 is a novel monocyte/macrophage endocytic receptor. Eur J Immunol 34:210–220CrossRefPubMedPubMedCentralGoogle Scholar
  4. Arumugam TV et al (2017) An atypical role for the myeloid receptor Mincle in central nervous system injury. J Cereb Blood Flow Metab 37:2098–2111CrossRefPubMedPubMedCentralGoogle Scholar
  5. Balch SG et al (1998) Cloning of a novel c-type lectin expressed by murine macrophages. J Biol Chem 273:18656–18664CrossRefPubMedPubMedCentralGoogle Scholar
  6. Behler F et al (2012) Role of Mincle in alveolar macrophage-dependent innate immunity against mycobacterial infections in mice. J Immunol 189:3121–3129CrossRefPubMedPubMedCentralGoogle Scholar
  7. Behler F et al (2015) Macrophage-inducible C-type lectin Mincle-expressing dendritic cells contribute to control of splenic Mycobacterium bovis BCG infection in mice. Infect Immun 83:184–196CrossRefPubMedPubMedCentralGoogle Scholar
  8. Behler-Janbeck F et al (2016) C-type lectin Mincle recognizes glucosyl-diacylglycerol of Streptococcus pneumoniae and plays a protective role in pneumococcal pneumonia. PLoS Pathog 12:e1006038CrossRefPubMedPubMedCentralGoogle Scholar
  9. Billeskov R et al (2016) Testing the H56 vaccine delivered in 4 different adjuvants as a BCG-booster in a non-human primate model of tuberculosis. PLoS ONE 11:e0161217CrossRefPubMedPubMedCentralGoogle Scholar
  10. Bird JH et al (2018) Synthesis of branched trehalose glycolipids and their Mincle agonist activity. J Org Chem 83:7593–7605CrossRefPubMedPubMedCentralGoogle Scholar
  11. Blank U et al (2009) Inhibitory ITAMs as novel regulators of immunity. Immunol Rev 232:59–71CrossRefPubMedPubMedCentralGoogle Scholar
  12. Bowker N et al (2016) Polymorphisms in the pattern recognition receptor Mincle gene (CLEC4E) and association with tuberculosis. Lung 194:763–767CrossRefPubMedPubMedCentralGoogle Scholar
  13. Braganza CD et al (1940) Identification and biological activity of synthetic macrophage inducible C-type lectin ligands. Front Immunol 2018:8Google Scholar
  14. Brown BR et al (2017) Fungal-derived cues promote ocular autoimmunity through a Dectin-2/Card9-mediated mechanism. Clin Exp Immunol 190:293–303CrossRefPubMedPubMedCentralGoogle Scholar
  15. Bugarcic A et al (2008) Human and mouse macrophage-inducible C-type lectin (Mincle) bind Candida albicans. Glycobiology 18:679–685CrossRefPubMedPubMedCentralGoogle Scholar
  16. Chinthamani S et al (2017) Macrophage inducible C-type lectin (Mincle) recognizes glycosylated surface (S)-layer of the periodontal pathogen Tannerella forsythia. PLoS ONE 12:e0173394CrossRefPubMedPubMedCentralGoogle Scholar
  17. Christensen D et al (1928) Seasonal influenza split vaccines confer partial cross-protection against heterologous influenza virus in ferrets when combined with the CAF01 adjuvant. Front Immunol 2018:8Google Scholar
  18. Christensen D et al (2009) Liposome-based cationic adjuvant formulations (CAF): past, present, and future. J Liposome Res 19:2–11CrossRefPubMedPubMedCentralGoogle Scholar
  19. Davidsen J et al (2005) Characterization of cationic liposomes based on dimethyldioctadecylammonium and synthetic cord factor from M. tuberculosis (trehalose 6,6’-dibehenate)-a novel adjuvant inducing both strong CMI and antibody responses. Biochim Biophys Acta 1718:22–31Google Scholar
  20. de Rivero Vaccari JC et al (2015) Mincle signaling in the innate immune response after traumatic brain injury. J Neurotrauma 32:228–236CrossRefPubMedPubMedCentralGoogle Scholar
  21. Decout A et al (2017) Rational design of adjuvants targeting the C-type lectin Mincle. Proc Natl Acad Sci U S A 114:2675–2680CrossRefPubMedPubMedCentralGoogle Scholar
  22. Desel C et al (2013) The Mincle-activating adjuvant TDB induces MyD88-dependent Th1 and Th17 responses through IL-1R signaling. PLoS ONE 8:e53531CrossRefPubMedPubMedCentralGoogle Scholar
  23. Devi S et al (2015) Induction of Mincle by Helicobacter pylori and consequent anti-inflammatory signaling denote a bacterial survival strategy. Sci Rep 5:15049CrossRefPubMedPubMedCentralGoogle Scholar
  24. Dietrich J et al (2014) Inducing dose sparing with inactivated polio virus formulated in adjuvant CAF01. PLoS ONE 9:e100879CrossRefPubMedPubMedCentralGoogle Scholar
  25. Feinberg H et al (2013) Mechanism for recognition of an unusual mycobacterial glycolipid by the macrophage receptor Mincle. J Biol Chem 288:28457–28465CrossRefPubMedPubMedCentralGoogle Scholar
  26. Feinberg H et al (2016) Binding sites for acylated trehalose analogs of glycolipid ligands on an extended carbohydrate recognition domain of the macrophage receptor Mincle. J Biol Chem 291:21222–21233CrossRefPubMedPubMedCentralGoogle Scholar
  27. Flornes LM et al (2004) Identification of lectin-like receptors expressed by antigen presenting cells and neutrophils and their mapping to a novel gene complex. Immunogenetics 56:506–517CrossRefPubMedPubMedCentralGoogle Scholar
  28. Flytzani S et al (2013) Anti-MOG antibodies are under polygenic regulation with the most significant control coming from the C-type lectin-like gene locus. Genes Immun 14(7):409–419CrossRefPubMedPubMedCentralGoogle Scholar
  29. Fomsgaard A et al (2011) Development and preclinical safety evaluation of a new therapeutic HIV-1 vaccine based on 18 T-cell minimal epitope peptides applying a novel cationic adjuvant CAF01. Vaccine 29:7067–7074CrossRefPubMedPubMedCentralGoogle Scholar
  30. Foster AJ et al (2018) Lipidated brartemicin analogues are potent Th1-stimulating vaccine adjuvants. J Med Chem 61:1045–1060CrossRefGoogle Scholar
  31. Furukawa A et al (2013) Structural analysis for glycolipid recognition by the C-type lectins Mincle and MCL. Proc Natl Acad Sci U S A 110:17438–17443CrossRefPubMedPubMedCentralGoogle Scholar
  32. Gram GJ et al (2009) A novel liposome-based adjuvant CAF01 for induction of CD8(+) cytotoxic T-lymphocytes (CTL) to HIV-1 minimal CTL peptides in HLA-A*0201 transgenic mice. PLoS ONE 4:e6950Google Scholar
  33. Greco SH et al (2016a) Mincle suppresses Toll-like receptor 4 activation. J Leukoc Biol 100:185–194CrossRefPubMedPubMedCentralGoogle Scholar
  34. Greco SH et al (2016b) Mincle signaling promotes con A Hepatitis. J Immunol 197:2816–2827CrossRefPubMedPubMedCentralGoogle Scholar
  35. Guo JP et al (2008) Profound and paradoxical impact on arthritis and autoimmunity of the rat antigen-presenting lectin-like receptor complex. Arthritis Rheum 58(5):1343–1353CrossRefGoogle Scholar
  36. Guo JP et al (2009) The rat antigen-presenting lectin-like receptor complex influences innate immunity and development of infectious diseases. Genes Immun 10:227–236CrossRefPubMedPubMedCentralGoogle Scholar
  37. Hansen J et al (2012) CAF05: cationic liposomes that incorporate synthetic cord factor and poly(I:C) induce CTL immunity and reduce tumor burden in mice. Cancer Immunol Immunother 61:893–903CrossRefPubMedPubMedCentralGoogle Scholar
  38. Hattori Y et al (2011) Glycerol monomycolate, a latent tuberculosis-associated mycobacterial lipid, induces eosinophilic hypersensitivity responses in guinea pigs. Biochem Biophys Res Commun 409:304–307Google Scholar
  39. Hattori Y et al (2014) Glycerol monomycolate is a novel ligand for the human, but not mouse macrophage inducible C-type lectin, Mincle. J Biol Chem 289:15405–15412CrossRefPubMedPubMedCentralGoogle Scholar
  40. He Y et al (2015) Macrophage-inducible C-type lectin/spleen tyrosine kinase signaling pathway contributes to neuroinflammation after subarachnoid hemorrhage in rats. Stroke 46:2277–2286CrossRefPubMedPubMedCentralGoogle Scholar
  41. Heitmann L et al (2013) Mincle is not essential for controlling Mycobacterium tuberculosis infection. Immunobiology 218:506–516CrossRefGoogle Scholar
  42. Hitzler I et al (2011) Dendritic cells prevent rather than promote immunity conferred by a helicobacter vaccine using a mycobacterial adjuvant. Gastroenterology 141:186–196CrossRefGoogle Scholar
  43. Holten-Andersen L et al (2004) Combination of the cationic surfactant dimethyl dioctadecyl ammonium bromide and synthetic mycobacterial cord factor as an efficient adjuvant for tuberculosis subunit vaccines. Infect Immun 72:1608–1617CrossRefPubMedPubMedCentralGoogle Scholar
  44. Honjoh C et al (2017) Association of C-type lectin Mincle with FcεRIβγ subunits leads to functional activation of RBL-2H3 cells through Syk. Sci Rep 7:46064CrossRefPubMedPubMedCentralGoogle Scholar
  45. Huber A et al (2016) Trehalose diester glycolipids are superior to the monoesters in binding to Mincle, activation of macrophages in vitro and adjuvant activity in vivo. Innate Immun 22:405–418CrossRefPubMedPubMedCentralGoogle Scholar
  46. Hupfer T et al (2016) Stat6-dependent inhibition of Mincle expression in mouse and human antigen-presenting cells by the Th2 cytokine IL-4. Front Immunol 7:423CrossRefPubMedPubMedCentralGoogle Scholar
  47. Iborra S et al (2016) Leishmania uses Mincle to target an inhibitory ITAM signaling pathway in dendritic cells that dampens adaptive immunity to infection. Immunity 45:788–801CrossRefPubMedPubMedCentralGoogle Scholar
  48. Ichioka M et al (2011) Increased expression of macrophage-inducible C-type lectin in adipose tissue of obese mice and humans. Diabetes 60:819–826CrossRefPubMedPubMedCentralGoogle Scholar
  49. Igarashi Y et al (2009) Brartemicin, an inhibitor of tumor cell invasion from the actinomycete Nonomuraea sp. J Nat Prod 72:980–982CrossRefGoogle Scholar
  50. Indrigo J et al (2003) Cord factor trehalose 6,6’-dimycolate (TDM) mediates trafficking events during mycobacterial infection of murine macrophages. Microbiology 149:2049–2059CrossRefGoogle Scholar
  51. Ishikawa E et al (2009) Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle. J Exp Med 206:2879–2888CrossRefPubMedPubMedCentralGoogle Scholar
  52. Ishikawa T et al (2013) Identification of distinct ligands for the C-type lectin receptors Mincle and Dectin-2 in the pathogenic fungus Malassezia. Cell Host Microbe 13:477–488CrossRefGoogle Scholar
  53. Jacobsen KM et al (2015) The natural product brartemicin is a high affinity ligand for the carbohydrate-recognition domain of the macrophage receptor mincle. Medchemcomm 6:647–652CrossRefPubMedPubMedCentralGoogle Scholar
  54. Jensen C et al (2017) Optimisation of a murine splenocyte mycobacterial growth inhibition assay using virulent Mycobacterium tuberculosis. Sci Rep 7:2830CrossRefPubMedPubMedCentralGoogle Scholar
  55. Kallerup RS et al (2015) Influence of trehalose 6,6’-diester (TDX) chain length on the physicochemical and immunopotentiating properties of DDA/TDX liposomes. Eur J Pharm Biopharm 90:80–89CrossRefGoogle Scholar
  56. Kamath AT et al (2012) Synchronization of dendritic cell activation and antigen exposure is required for the induction of Th1/Th17 responses. J Immunol 188:4828–4837CrossRefGoogle Scholar
  57. Karlsson I et al (2013) Adjuvanted HLA-supertype restricted subdominant peptides induce new T-cell immunity during untreated HIV-1-infection. Clin Immunol 146:120–130CrossRefGoogle Scholar
  58. Kaur R et al (2012) Pegylation of DDA: TDB liposomal adjuvants reduces the vaccine depot effect and alters the Th1/Th2 immune responses. J Control Release 158:72–77CrossRefGoogle Scholar
  59. Kawata K et al (2012) Mincle and human B cell function. J Autoimmun 39:315–322CrossRefPubMedPubMedCentralGoogle Scholar
  60. Kerscher B et al (2013) The Dectin-2 family of C-type lectin-like receptors: an update. Int Immunol 25:271–277CrossRefPubMedPubMedCentralGoogle Scholar
  61. Kerscher B et al (2016a) Signalling through MyD88 drives surface expression of the mycobacterial receptors MCL (Clecsf8, Clec4d) and Mincle (Clec4e) following microbial stimulation. Microbes Infec 18:505–509CrossRefGoogle Scholar
  62. Kerscher B et al (2016b) Mycobacterial receptor, Clec4d (CLECSF8, MCL), is coregulated with Mincle and upregulated on mouse myeloid cells following microbial challenge. Eur J Immunol 46:381–389CrossRefPubMedPubMedCentralGoogle Scholar
  63. Khan AA et al (2011) Long-chain lipids are required for the innate immune recognition of trehalose diesters by macrophages. ChemBioChem 12:2572–2576CrossRefPubMedPubMedCentralGoogle Scholar
  64. Kim SH et al (2017) Expression of C-type lectin receptor mRNA in chronic otitis media with cholesteatoma. Acta Otolaryngol 137:581–587CrossRefPubMedPubMedCentralGoogle Scholar
  65. Kim JW et al (2018) Spliceosome-associated protein 130 exacerbates alcohol-induced liver injury by inducing NLRP3 inflammasome-mediated IL-1β in mice. Am J Pathol 188:967–980CrossRefPubMedPubMedCentralGoogle Scholar
  66. Kiyotake R et al (2015) Human Mincle binds to cholesterol crystals and triggers innate immune responses. J Biol Chem 290:25322–25332CrossRefPubMedPubMedCentralGoogle Scholar
  67. Kodar K et al (2015) The uptake of trehalose glycolipids by macrophages is independent of Mincle. ChemBioChem 16:683–693CrossRefPubMedPubMedCentralGoogle Scholar
  68. Kodar K et al (2017) The Mincle ligand trehalose dibehenate differentially modulates M1-like and M2-like macrophage phenotype and function via Syk signaling. Immun Inflamm Dis 5:503–514CrossRefPubMedPubMedCentralGoogle Scholar
  69. Korsholm KS et al (2014) Induction of CD8+ T-cell responses against subunit antigens by the novel cationic liposomal CAF09 adjuvant. Vaccine 32:3927–3935CrossRefPubMedPubMedCentralGoogle Scholar
  70. Kostarnoy AV et al (2017) Receptor Mincle promotes skin allergies and is capable of recognizing cholesterol sulfate. Proc Natl Acad Sci U S A 114:E2758–E2765CrossRefPubMedPubMedCentralGoogle Scholar
  71. Kottom TJ et al (2017) The interaction of pneumocystis with the C-type lectin receptor Mincle exerts a significant role in host defense against infection. J Immunol 198:3515–3525CrossRefPubMedPubMedCentralGoogle Scholar
  72. Leal JM et al (2015) Intranasal vaccination with killed Leishmania amazonensis promastigotes antigen (LaAg) associated with CAF01 adjuvant induces partial protection in BALB/c mice challenged with Leishmania (infantum) chagasi. Parasitology 142:1640–1646CrossRefPubMedPubMedCentralGoogle Scholar
  73. Lee WB et al (2012) Neutrophils promote mycobacterial trehalose dimycolate-induced lung inflammation via the Mincle pathway. PLoS Pathog 8:e1002614Google Scholar
  74. Lee WB et al (2016) Mincle-mediated translational regulation is required for strong nitric oxide production and inflammation resolution. Nat Commun 7:11322Google Scholar
  75. Lee WB et al (2017) Mincle activation enhances neutrophil migration and resistance to polymicrobial septic peritonitis. Sci Rep 7:41106Google Scholar
  76. Lee EJ et al (2016) Mincle activation and the Syk/Card9 signaling axis are central to the development of autoimmune disease of the eye. J Immunol 196:3148–3158CrossRefPubMedPubMedCentralGoogle Scholar
  77. Li H et al (1998) Peripheral-type benzodiazepine receptor function in cholesterol transport. Identification of a putative cholesterol recognition/interaction amino acid sequence and consensus pattern. Endocrinology 139:4991–4997Google Scholar
  78. Lin J et al (2017) Mincle inhibits neutrophils and macrophages apoptosis in A. fumigatus keratitis. Int Immunopharmacol 52:101–109Google Scholar
  79. Lindenstrøm T et al (2009) Tuberculosis subunit vaccination provides long-term protective immunity characterized by multifunctional CD4 memory T cells. J Immunol 182:8047–8055CrossRefPubMedPubMedCentralGoogle Scholar
  80. Lindenstrøm T et al (2012) Vaccine-induced th17 cells are maintained long-term postvaccination as a distinct and phenotypically stable memory subset. Infect Immun 80:3533–3544CrossRefPubMedPubMedCentralGoogle Scholar
  81. Liu D et al (2018) Sophora flavescens protects against mycobacterial trehalose dimycolate-induced lung granuloma by inhibiting inflammation and infiltration of macrophages. Sci Rep 8:3903CrossRefPubMedPubMedCentralGoogle Scholar
  82. Lorentzen JC et al (2007) Association of arthritis with a gene complex encoding C-type lectin-like receptors. Arthritis Rheum 56(8):2620–2632CrossRefPubMedPubMedCentralGoogle Scholar
  83. Lv LL et al (2017) The pattern recognition receptor, Mincle, is essential for maintaining the M1 macrophage phenotype in acute renal inflammation. Kidney Int 91:587–602CrossRefPubMedPubMedCentralGoogle Scholar
  84. Ma D et al (2011) Purification and characterization of two new allergens from the salivary glands of the horsefly, Tabanus yao. Allergy 66:101–109CrossRefPubMedPubMedCentralGoogle Scholar
  85. Martel CJ et al (2011) CAF01 potentiates immune responses and efficacy of an inactivated influenza vaccine in ferrets. PLoS ONE 6:e22891Google Scholar
  86. Matsumoto M et al (1999) A novel LPS-inducible C-type lectin is a transcriptional target of NF-IL6 in macrophages. J Immunol 163:5039–5048PubMedPubMedCentralGoogle Scholar
  87. Matsunaga I et al (2008) Mycolyltransferase-mediated glycolipid exchange in mycobacteria. J Biol Chem 283:28835–28841CrossRefPubMedPubMedCentralGoogle Scholar
  88. Miyake Y et al (2013) C-type lectin MCL is an FcRγ-coupled receptor that mediates the adjuvanticity of mycobacterial cord factor. Immunity 1050–1062Google Scholar
  89. Miyake Y et al (2015) C-type lectin receptor MCL facilitates Mincle expression and signaling through complex formation. J Immunol 194:5366–5374CrossRefPubMedPubMedCentralGoogle Scholar
  90. Mortensen R et al (2017) Local Th17/IgA immunity correlate with protection against intranasal infection with Streptococcus pyogenes. PLoS ONE 12:e0175707CrossRefPubMedPubMedCentralGoogle Scholar
  91. Nagata M et al (2017) Intracellular metabolite β-glucosylceramide is an endogenous Mincle ligand possessing immunostimulatory activity. Proc Natl Acad Sci U S A 114:E3285–E3294CrossRefPubMedPubMedCentralGoogle Scholar
  92. Nakamura N et al (2006) Isolation and expression profiling of genes upregulated in bone marrow-derived mononuclear cells of rheumatoid arthritis patients. DNA Res 13(4):169–183CrossRefPubMedPubMedCentralGoogle Scholar
  93. Nordly P et al (2011a) Incorporation of the TLR4 agonist monophosphoryl lipid A into the bilayer of DDA/TDB liposomes: physico-chemical characterization and induction of CD8+ T-cell responses in vivo. Pharm Res 28:553–562CrossRefPubMedPubMedCentralGoogle Scholar
  94. Nordly P et al (2011b) Immunity by formulation design: induction of high CD8+ T-cell responses by poly(I:C) incorporated into the CAF01 adjuvant via a double emulsion method. J Control Release 150:307–317CrossRefPubMedPubMedCentralGoogle Scholar
  95. Olsen AW et al (2010) Protection against Chlamydia promoted by a subunit vaccine (CTH1) compared with a primary intranasal infection in a mouse genital challenge model. PLoS ONE 5:e10768Google Scholar
  96. Olsen AW et al (2017) Protective effect of vaccine promoted neutralizing antibodies against the intracellular pathogen Chlamydia trachomatis. Front Immunol 8:1652Google Scholar
  97. Ostrop J et al (2015) Contribution of MINCLE-SYK signaling to activation of primary human APCs by mycobacterial cord factor and the novel adjuvant TDB. J Immunol 195:2417–2428CrossRefPubMedPubMedCentralGoogle Scholar
  98. Patin EC et al (2017) Trehalose dimycolate interferes with FcγR-mediated phagosome maturation through Mincle, SHP-1 and FcγRIIB signalling. PLoS ONE 12:e0174973Google Scholar
  99. Patin EC et al (2016) Mincle-mediated anti-inflammatory IL-10 response counter-regulates IL-12 in vitro. Innate Immun 22:181–185CrossRefPubMedPubMedCentralGoogle Scholar
  100. Pimm MV et al (1979) Immunotherapy of an ascitic rat hepatoma with cord factor (trehalose-6, 6′-dimycolate) and synthetic analogues. Int J Cancer 24:780–785CrossRefPubMedPubMedCentralGoogle Scholar
  101. Pinto VV et al (2012) The effect of adjuvants on the immune response induced by a DBL4ɛ-ID4 VAR2CSA based Plasmodium falciparum vaccine against placental malaria. Vaccine 30:572–579CrossRefPubMedPubMedCentralGoogle Scholar
  102. 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:e0117022CrossRefPubMedPubMedCentralGoogle Scholar
  103. Rambaruth ND et al (2015) Mouse Mincle: characterization as a model for human Mincle and evolutionary implications. Molecules 20:6670–6682CrossRefPubMedPubMedCentralGoogle Scholar
  104. Ribeiro-Gomes FL et al (2012) Efficient capture of infected neutrophils by dendritic cells in the skin inhibits the early anti-leishmania response. PLoS Pathog 8:e1002536Google Scholar
  105. Richardson MB et al (2015) Mycobacterium tuberculosis β-gentiobiosyl diacylglycerides signal through the pattern recognition receptor Mincle: total synthesis and structure activity relationships. Chem Commun (Camb) 51:15027–15030CrossRefGoogle Scholar
  106. Román VR et al (2013) Therapeutic vaccination using cationic liposome-adjuvanted HIV type 1 peptides representing HLA-supertype-restricted subdominant T cell epitopes: safety, immunogenicity, and feasibility in Guinea-Bissau. AIDS Res Hum Retroviruses 29:1504–1512CrossRefPubMedPubMedCentralGoogle Scholar
  107. Roperto S et al (2015) Mincle, an innate immune receptor, is expressed in urothelial cancer cells of papillomavirus-associated urothelial tumors of cattle. PLoS ONE 10:e0141624CrossRefPubMedPubMedCentralGoogle Scholar
  108. Rosenkrands I et al (2011) Enhanced humoral and cell-mediated immune responses after immunization with trivalent influenza vaccine adjuvanted with cationic liposomes. Vaccine 29:6283–6291CrossRefPubMedPubMedCentralGoogle Scholar
  109. Ryll R et al (2001) Immunological properties of trehalose dimycolate (cord factor) and other mycolic acid-containing glycolipids—a review. Microbiol Immunol 45:801–811CrossRefPubMedPubMedCentralGoogle Scholar
  110. Schick J et al (2017) Toll-like receptor 2 and Mincle cooperatively sense corynebacterial cell wall glycolipids. Infect Immun 85:e00075–17CrossRefPubMedPubMedCentralGoogle Scholar
  111. Schoenen H et al (2010) Cutting edge: Mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analog trehalose-dibehenate. J Immunol 184:2756–2760CrossRefPubMedPubMedCentralGoogle Scholar
  112. Schoenen H et al (2014) Differential control of Mincle-dependent cord factor recognition and macrophage responses by the transcription factors C/EBPβ and HIF1α. J Immunol 193:3664–3675CrossRefPubMedPubMedCentralGoogle Scholar
  113. Schweneker K et al (2013) The mycobacterial cord factor adjuvant analogue trehalose-6,6’-dibehenate (TDB) activates the Nlrp3 inflammasome. Immunobiology 218:664–673CrossRefPubMedPubMedCentralGoogle Scholar
  114. Seifert L et al (2016) The necrosome promotes pancreatic oncogenesis via CXCL1 and MINCLE-induced immune suppression. Nature 532:245–249CrossRefPubMedPubMedCentralGoogle Scholar
  115. Shah S et al (2016) Total synthesis of a cyclopropane-fatty acid α-glucosyl diglyceride from Lactobacillus plantarum and identification of its ability to signal through Mincle. Chem Commun (Camb) 52:10902–10905CrossRefGoogle Scholar
  116. Sharma A et al (2014) Protective role of Mincle in bacterial pneumonia by regulation of neutrophil mediated phagocytosis and extracellular trap formation. J Infect Dis 209:1837–1846CrossRefPubMedPubMedCentralGoogle Scholar
  117. Sharma A et al (2017) Mincle-mediated neutrophil extracellular trap formation by regulation of autophagy. J Infect Dis 215:1040–1048CrossRefPubMedPubMedCentralGoogle Scholar
  118. Söldner CA et al (2018) Interaction of glycolipids with the macrophage surface receptor Mincle—a systematic molecular dynamics study. Sci Rep 8:5374Google Scholar
  119. Sousa Mda G et al (2011) Restoration of pattern recognition receptor costimulation to treat chromoblastomycosis, a chronic fungal infection of the skin. Cell Host Microbe 9:436–443CrossRefGoogle Scholar
  120. Stamm CE et al (2015) Sensing of Mycobacterium tuberculosis and consequences to both host and bacillus. Immunol Rev 264:204–219CrossRefPubMedPubMedCentralGoogle Scholar
  121. Stocker BL et al (2014) On one leg: trehalose monoesters activate macrophages in a Mincle-dependant manner. ChemBioChem 15:382–388CrossRefPubMedPubMedCentralGoogle Scholar
  122. Suzuki Y et al (2013) Involvement of Mincle and Syk in the changes to innate immunity after ischemic stroke. Sci Rep 3:3177CrossRefPubMedPubMedCentralGoogle Scholar
  123. Tanaka M et al (2014) Macrophage-inducible C-type lectin underlies obesity-induced adipose tissue fibrosis. Nat Commun 5:4982CrossRefPubMedPubMedCentralGoogle Scholar
  124. Thakur A et al (2013) Cell-mediated and humoral immune responses after immunization of calves with a recombinant multiantigenic Mycobacterium avium subsp. paratuberculosis subunit vaccine at different ages. Clin Vaccine Immunol 20:551–558Google Scholar
  125. Tima HG et al (2017) Inflammatory properties and adjuvant potential of synthetic glycolipids homologous to mycolate esters of the cell wall of Mycobacterium tuberculosis. J Innate Immun 9:162–180CrossRefPubMedPubMedCentralGoogle Scholar
  126. Toyonaga K et al (2014) Characterization of the receptors for mycobacterial cord factor in Guinea pig. PLoS ONE 9:e88747CrossRefPubMedPubMedCentralGoogle Scholar
  127. Toyonaga K et al (2016) C-type Lectin receptor DCAR recognizes mycobacterial phosphatidyl-inositol mannosides to promote a Th1 response during infection. Immunity 45:1245–1257CrossRefPubMedPubMedCentralGoogle Scholar
  128. Troegeler A et al (2017) C-type lectin receptor DCIR modulates immunity to tuberculosis by sustaining type I interferon signaling in dendritic cells. Proc Natl Acad Sci U S A 114:E540–E549CrossRefPubMedPubMedCentralGoogle Scholar
  129. Van der Peet PL et al (2015) Corynomycolic acid-containing glycolipids signal through the pattern recognition receptor Mincle. Chem Commun (Camb) 51:5100–5103CrossRefGoogle Scholar
  130. van Dissel JT et al (2014) A novel liposomal adjuvant system, CAF01, promotes long-lived Mycobacterium tuberculosis-specific T-cell responses in human. Vaccine 32:7098–7107CrossRefPubMedPubMedCentralGoogle Scholar
  131. Van Haren SD et al (2016) Age-specific adjuvant synergy: Dual TLR7/8 and Mincle activation of human newborn dendritic cells enables Th1 polarization. J Immunol 197:4413–4424CrossRefPubMedPubMedCentralGoogle Scholar
  132. Vijayan D et al (2012) Mincle polarizes human monocyte and neutrophil responses to Candida albicans. Immunol Cell Biol 90:889–895CrossRefPubMedPubMedCentralGoogle Scholar
  133. Vono M et al (2018) Overcoming the neonatal limitations of inducing germinal centers through liposome-based adjuvants including C-type lectin agonists trehalose dibehenate or curdlan. Front Immunol 9:381CrossRefPubMedPubMedCentralGoogle Scholar
  134. Watanabe Y et al (2016) Isoliquiritigenin attenuates adipose tissue inflammation in vitro and adipose tissue fibrosis through inhibition of innate immune responses in mice. Sci Rep 6:23097CrossRefPubMedPubMedCentralGoogle Scholar
  135. Weis WI et al (1998) The C-type lectin superfamily in the immune system. Immunol Rev 163:19–34CrossRefGoogle Scholar
  136. 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 180:7404–7413CrossRefGoogle Scholar
  137. Wevers BA et al (2014) Fungal engagement of the C-type lectin Mincle suppresses Dectin-1-induced antifungal immunity. Cell Host Microbe 15:494–505CrossRefGoogle Scholar
  138. Williams SJ (2017) Sensing lipids with Mincle: structure and function. Front Immunol 8:1662CrossRefPubMedPubMedCentralGoogle Scholar
  139. Wilson GJ et al (2015) The C-type lectin receptor CLECSF8/CLEC4D is a key component of anti-mycobacterial immunity. Cell Host Microbe 17:252–259CrossRefPubMedPubMedCentralGoogle Scholar
  140. Wu XY et al (2012) Macrophage-inducible C-type lectin is associated with anti-cyclic citrullinated peptide antibodies-positive rheumatoid arthritis in men. Chin Med J (Engl) 125:3115–3119Google Scholar
  141. Xie Y et al (2017) Human albumin attenuates excessive innate immunity via inhibition of microglial Mincle/Syk signaling in subarachnoid hemorrhage. Brain Behav Immun 60:346–360CrossRefGoogle Scholar
  142. Yamasaki S (2013) Signaling while eating: MCL is coupled with Mincle. Eur J Immunol 43:3167–3174CrossRefGoogle Scholar
  143. Yamasaki S et al (2008) Mincle is an ITAM-coupled activating receptor that senses damaged cells. Nat Immunol 9:1179–1188CrossRefPubMedPubMedCentralGoogle Scholar
  144. Yamasaki S et al (2009) C-type lectin Mincle is an activating receptor for pathogenic fungus, Malassezia. Proc Natl Acad Sci U S A 106:1897–1902CrossRefPubMedPubMedCentralGoogle Scholar
  145. Yonekawa A et al (2014) Dectin-2 is a direct receptor for mannose-capped lipoarabinomannan of mycobacteria. Immunity 41:402–413CrossRefPubMedPubMedCentralGoogle Scholar
  146. Yu H et al (2010) Chlamydia muridarum T-cell antigens formulated with the adjuvant DDA/TDB induce immunity against infection that correlates with a high frequency of gamma interferon (IFN-gamma)/tumor necrosis factor alpha and IFN-gamma/interleukin-17 double-positive CD4+ T cells. Infect Immun 78:2272–2282CrossRefPubMedPubMedCentralGoogle Scholar
  147. Yu GR et al (2018) Mincle in the innate immune response of mice fungal keratitis. Int J Ophthalmol 11:539–547PubMedPubMedCentralGoogle Scholar
  148. Zhang XQ et al (2014) C-type lectin receptor Dectin-3 mediates trehalose 6,6′-Dimycolate (TDM)-induced Mincle expression through CARD9/Bcl10/MALT1-dependent nuclear factor (NF)-κB activation. J Biol Chem 289:30052–30062CrossRefGoogle Scholar
  149. Zhang Q et al (2018) Integrin CD11b negatively regulates Mincle-induced signaling via the Lyn-SIRPα-SHP1 complex. Exp Mol Med 50:e439CrossRefPubMedPubMedCentralGoogle Scholar
  150. Zheng RB et al (2017) Insights into Interactions of mycobacteria with the host innate immune system from a novel array of synthetic mycobacterial glycans. ACS Chem Biol 12:2990–3002CrossRefPubMedPubMedCentralGoogle Scholar
  151. Zhou H et al (2016) IRAKM-Mincle axis links cell death to inflammation: pathophysiological implications for chronic alcoholic liver disease. Hepatology 64:1978–1993CrossRefPubMedPubMedCentralGoogle Scholar
  152. Zoccola E et al (2017) Immune transcriptome reveals the Mincle C-type lectin receptor acts as a partial replacement for TLR4 in lipopolysaccharide-mediated inflammatory response in barramundi (Lates calcarifer). Mol Immunol 83:33–45CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2020

Authors and Affiliations

  1. 1.Division of Molecular and Cellular Immunoscience, Department of Biomolecular Sciences, Faculty of MedicineSaga UniversitySagaJapan
  2. 2.Department of Molecular Immunology, Research Institute for Microbial DiseasesOsaka UniversitySuitaJapan
  3. 3.Laboratory of Molecular Immunology, Immunology Frontier Research CenterOsaka UniversityOsakaJapan

Personalised recommendations