Abstract
Mycobacteria have unique lipids on their cell walls, and the structures and physiological activities of these lipid components have been the subject of many studies. Although the host receptors for mycobacterial lipid have long been elusive, in recent years C-type lectin receptors (CLRs) have been reported to recognize these components. The dendritic cell immunoactivating receptor (DCAR), a CLR member, is encoded by Clec4b1. DCAR, which was identified in 2003, is reported to be associated with the immunoreceptor tyrosine-based activation motif (ITAM)-containing adaptor protein, the Fc receptor γ chain (FcRγ). However, its physiological ligand and biological function were unknown. We recently identified DCAR as an activating receptor for mycobacteria. DCAR recognizes acylated phosphatidyl-inositol mannosides (PIMs) in mycobacteria to promote Th1 responses during mycobacterial infection. This review summarizes recent discoveries about the ligands and immunological roles of DCAR.
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References
Ainge GD, Parlane NA, Denis M et al (2006) Phosphatidylinositol mannosides: synthesis and adjuvant properties of phosphatidylinositol di- and tetramannosides. Bioorg Med Chem 14(22):7615–7624. https://doi.org/10.1016/j.bmc.2006.07.003
Bain CC, Hawley CA, Garner H et al (2016) Long-lived self-renewing bone marrow-derived macrophages displace embryo-derived cells to inhabit adult serous cavities. Nat Commun 7:ncomms11852. https://doi.org/10.1038/ncomms11852
Bansal K, Kapoor N, Narayana Y et al (2009) PIM2 Induced COX-2 and MMP-9 expression in macrophages requires PI3K and Notch1 signaling. PLoS ONE 4(3):e4911. https://doi.org/10.1371/journal.pone.0004911
Bates EE, Fournier N, Garcia E et al (1999) APCs express DCIR, a novel C-type lectin surface receptor containing an immunoreceptor tyrosine-based inhibitory motif. J Immunol 163(4):1973–1983
Brown GD, Willment JA, Whitehead L (2018) C-type lectins in immunity and homeostasis. Nat Rev Immunol 18(6):374–389. https://doi.org/10.1038/s41577-018-0004-8
Cain DW, O’Koren EG, Kan MJ et al (2013) Identification of a tissue-specific, C/EBPbeta-dependent pathway of differentiation for murine peritoneal macrophages. J Immunol 191(9):4665–4675. https://doi.org/10.4049/jimmunol.1300581
Cooper AM (2009) Cell-mediated immune responses in tuberculosis. Annu Rev Immunol 27:393–422. https://doi.org/10.1146/annurev.immunol.021908.132703
Crellin PK, Luo C-Y, Morita YS (2013) Metabolism of plasma membrane lipids in mycobacteria and corynebacteria. Lipid Metabolism 6:119–148
Dambuza IM, Brown GD (2015) C-type lectins in immunity: recent developments. Curr Opin Immunol 32:21–27. https://doi.org/10.1016/j.coi.2014.12.002
Domingo-Gonzalez R, Prince O, Cooper A et al (2016) Cytokines and chemokines in Mycobacterium tuberculosis infection. Microbiol Spectr 4(5). https://doi.org/10.1128/microbiolspec.tbtb2-0018-2016
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. https://doi.org/10.1016/j.sbi.2015.06.003
Driessen NN, Ummels R, Maaskant JJ et al (2009) Role of phosphatidylinositol mannosides in the interaction between mycobacteria and DC-SIGN. Infect Immun 77(10):4538–4547. https://doi.org/10.1128/IAI.01256-08
Fischer K, Scotet E, Niemeyer M et al (2004) Mycobacterial phosphatidylinositol mannoside is a natural antigen for CD1d-restricted T cells. Proc Natl Acad Sci USA 101(29):10685–10690. https://doi.org/10.1073/pnas.0403787101
Gautier EL, Ivanov S, Lesnik P et al (2013) Local apoptosis mediates clearance of macrophages from resolving inflammation in mice. Blood 122(15):2714–2722. https://doi.org/10.1182/blood-2013-01-478206
Ghosn EE, Cassado AA, Govoni GR et al (2010) Two physically, functionally, and developmentally distinct peritoneal macrophage subsets. Proc Natl Acad Sci USA 107(6):2568–2573. https://doi.org/10.1073/pnas.0915000107
Gilleron M, Ronet C, Mempel M et al (2001) Acylation state of the phosphatidylinositol mannosides from Mycobacterium bovis bacillus Calmette Guerin and ability to induce granuloma and recruit natural killer T cells. J Biol Chem 276(37):34896–34904. https://doi.org/10.1074/jbc.M103908200
Gilleron M, Quesniaux VF, Puzo G (2003) Acylation state of the phosphatidylinositol hexamannosides from Mycobacterium bovis bacillus Calmette Guerin and mycobacterium tuberculosis H37Rv and its implication in toll-like receptor response. J Biol Chem 278(32):29880–29889. https://doi.org/10.1074/jbc.M303446200
Gonzalez-Juarrero M, Shim TS, Kipnis A et al (2003) Dynamics of macrophage cell populations during murine pulmonary tuberculosis. J Immunol 171(6):3128–3135
Guerin ME, Kordulakova J, Alzari PM et al (2010) Molecular basis of phosphatidyl-myo-inositol mannoside biosynthesis and regulation in mycobacteria. J Biol Chem 285(44):33577–33583. https://doi.org/10.1074/jbc.R110.168328
Hardison SE, Brown GD (2012) C-type lectin receptors orchestrate antifungal immunity. Nat Immunol 13(9):817–822. https://doi.org/10.1038/ni.2369
Ishikawa E, Ishikawa T, Morita YS et al (2009) Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle. J Exp Med 206(13):2879–2888. https://doi.org/10.1084/jem.20091750
Ishikawa E, Mori D, Yamasaki S (2017) Recognition of mycobacterial lipids by immune receptors. Trends Immunol 38(1):66–76. https://doi.org/10.1016/j.it.2016.10.009
Jackson M (2014) The mycobacterial cell envelope-lipids. Cold Spring Harb Perspect Med 4(10). https://doi.org/10.1101/cshperspect.a021105
Jones BW, Heldwein KA, Means TK et al (2001) Differential roles of toll-like receptors in the elicitation of proinflammatory responses by macrophages. Ann Rheum Dis 60 Suppl 3:iii6–12
Kanazawa N, Okazaki T, Nishimura H et al (2002) DCIR acts as an inhibitory receptor depending on its immunoreceptor tyrosine-based inhibitory motif. J Invest Dermatol 118(2):261–266. https://doi.org/10.1046/j.0022-202x.2001.01633.x
Kanazawa N, Tashiro K, Inaba K et al (2003) Dendritic cell immunoactivating receptor, a novel C-type lectin immunoreceptor, acts as an activating receptor through association with Fc receptor gamma chain. J Biol Chem 278(35):32645–32652. https://doi.org/10.1074/jbc.M304226200
Kanazawa N, Tashiro K, Miyachi Y (2004) Signaling and immune regulatory role of the dendritic cell immunoreceptor (DCIR) family lectins: DCIR, DCAR, dectin-2 and BDCA-2. Immunobiology 209(1–2):179–190. https://doi.org/10.1016/j.imbio.2004.03.004
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. https://doi.org/10.1016/j.jdermsci.2006.09.001
Kawai T, Akira S (2010) The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 11(5):373–384. https://doi.org/10.1038/ni.1863
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. https://doi.org/10.1093/intimm/dxt006
Kim KW, Williams JW, Wang YT et al (2016) MHC II+ resident peritoneal and pleural macrophages rely on IRF4 for development from circulating monocytes. J Exp Med 213(10):1951–1959. https://doi.org/10.1084/jem.20160486
Kishimoto A, Watanabe M, Terauchi K et al (2015) Ubiquitous versus restricted expression of the two mouse dendritic cell C-type lectin receptors, DCIR1 and DCAR2, among myeloid cells. Biochem Biophys Res Commun. https://doi.org/10.1016/j.bbrc.2015.09.146
Liao CT, Rosas M, Davies LC et al (2016) IL-10 differentially controls the infiltration of inflammatory macrophages and antigen-presenting cells during inflammation. Eur J Immunol 46(9):2222–2232. https://doi.org/10.1002/eji.201646528
Marakalala MJ, Ndlovu H (2017) Signaling C-type lectin receptors in antimycobacterial immunity. PLoS Pathog 13(6):e1006333. https://doi.org/10.1371/journal.ppat.1006333
Minnikin DE, Lee OY, Wu HH et al (2015) Pathophysiological implications of cell envelope structure in Mycobacterium tuberculosis and related taxa. In: Tuberculosis-expanding knowledge, pp 145–175
Miyake Y, Toyonaga K, Mori D et al (2013) C-type lectin MCL is an FcRgamma-coupled receptor that mediates the adjuvanticity of mycobacterial cord factor. Immunity 38(5):1050–1062. https://doi.org/10.1016/j.immuni.2013.03.010
Monin L, Khader SA (2014) Chemokines in tuberculosis: the good, the bad and the ugly. Semin Immunol 26(6):552–558. https://doi.org/10.1016/j.smim.2014.09.004
Nigou J, Gilleron M, Puzo G (2003) Lipoarabinomannans: from structure to biosynthesis. Biochimie 85(1–2):153–166
Parlane NA, Compton BJ, Hayman CM et al (2012) Phosphatidylinositol di-mannoside and derivates modulate the immune response to and efficacy of a tuberculosis protein vaccine against Mycobacterium bovis infection. Vaccine 30(3):580–588. https://doi.org/10.1016/j.vaccine.2011.11.055
Patil PS, Cheng TJ, Zulueta MM et al (2015) Total synthesis of tetraacylated phosphatidylinositol hexamannoside and evaluation of its immunomodulatory activity. Nat Commun 6:7239. https://doi.org/10.1038/ncomms8239
Peters W, Scott HM, Chambers HF et al (2001) Chemokine receptor 2 serves an early and essential role in resistance to Mycobacterium tuberculosis. Proc Natl Acad Sci USA 98(14):7958–7963. https://doi.org/10.1073/pnas.131207398
Sancho D, Reis e Sousa C (2012) Signaling by myeloid C-type lectin receptors in immunity and homeostasis. Annu Rev Immunol 30:491–529. https://doi.org/10.1146/annurev-immunol-031210-101352
Shiokawa M, Yamasaki S, Saijo S (2017) C-type lectin receptors in anti-fungal immunity. Curr Opin Microbiol 40:123–130. https://doi.org/10.1016/j.mib.2017.11.004
Sprott GD, Dicaire CJ, Gurnani K et al (2004) Activation of dendritic cells by liposomes prepared from phosphatidylinositol mannosides from Mycobacterium bovis bacillus Calmette-Guerin and adjuvant activity in vivo. Infect Immun 72(9):5235–5246. https://doi.org/10.1128/IAI.72.9.5235-5246.2004
T’Jonck W, Guilliams M, Bonnardel J (2018) Niche signals and transcription factors involved in tissue-resident macrophage development. Cell Immunol 330:43–53. https://doi.org/10.1016/j.cellimm.2018.02.005
Takeuchi O, Akira S (2010) Pattern recognition receptors and inflammation. Cell 140(6):805–820. https://doi.org/10.1016/j.cell.2010.01.022
Takimoto H, Maruyama H, Shimada KI et al (2006) Interferon-gamma independent formation of pulmonary granuloma in mice by injections with trehalose dimycolate (cord factor), lipoarabinomannan and phosphatidylinositol mannosides isolated from Mycobacterium tuberculosis. Clin Exp Immunol 144(1):134–141. https://doi.org/10.1111/j.1365-2249.2006.03043.x
Torrelles JB, Azad AK, Schlesinger LS (2006) Fine discrimination in the recognition of individual species of phosphatidyl-myo-inositol mannosides from Mycobacterium tuberculosis by C-type lectin pattern recognition receptors. J Immunol 177(3):1805–1816
Toyonaga K, Torigoe S, Motomura Y et al (2016) C-Type lectin receptor DCAR recognizes mycobacterial phosphatidyl-inositol Mannosides to promote a Th1 response during infection. Immunity 45(6):1245–1257. https://doi.org/10.1016/j.immuni.2016.10.012
Troegeler A, Mercier I, Cougoule C 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 USA 114(4):E540–E549. https://doi.org/10.1073/pnas.1613254114
Yonekawa A, Saijo S, Hoshino Y et al (2014) Dectin-2 is a direct receptor for mannose-capped lipoarabinomannan of mycobacteria. Immunity 41(3):402–413. https://doi.org/10.1016/j.immuni.2014.08.005
Zelensky AN, Gready JE (2005) The C-type lectin-like domain superfamily. FEBS J 272(24):6179–6217. https://doi.org/10.1111/j.1742-4658.2005.05031.x
Zheng RB, Jegouzo SAF, Joe M 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(12):2990–3002. https://doi.org/10.1021/acschembio.7b00797
Zheng T, Luo D, Compton B et al (2015) Adjuvanticity of a synthetic phosphatidylinositol dimannoside to a subvirion influenza vaccine in an influenza mouse model. J Vaccines Vaccin 6(2):277
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We thank Sandra Cheesman, Ph.D., from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.
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Toyonaga, K., Yamasaki, S. (2020). Recognition of Mycobacteria by Dendritic Cell Immunoactivating Receptor. In: Yamasaki, S. (eds) C-Type Lectins in Immune Homeostasis. Current Topics in Microbiology and Immunology, vol 429. Springer, Cham. https://doi.org/10.1007/82_2020_203
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