Macrophage inducible Ca2+-dependent lectin receptor, (abbreviated to Mincle), is a member of the C-type lectin superfamily encoded by the gene CLEC4E. It is a pattern recognition receptor that can recognize glycolipids including mycobacterial cord factor, trehalose-6,6'-dimycolate (TDM).[1][2] The mincle receptor binds a range of carbohydrate structures, predominantly containing glucose or mannose, and play an important role in recognition of bacterial glycolipids by the immune system. Upon activation by cord factor, Mincle binds the Fc receptor FcRγ and Syk. Cord factor also binds and activates the related C-type lectin MCL.[3][4] Upon receptor stimulation is PKC-δ activated, which subsequently phosphorylates CARD9 that triggers recruitment of BCL10 and MALT1, leading to a CARD-CC/BCL10/MALT1 (CBM) signaling complex. [5] This signaling complex in turn triggers downstream recruitment of TRAF6 and NF-κB activation.

A wide range of ligands promote signalling through Mincle, including proteins, sterols and glycolipids from altered or damaged self, and various glycolipids from pathogenic and commensal organisms.

Mincle agonists from self

Crystalline cholesterol, which accumulates in atherosclerotic lesions, can signal through human Mincle.[6] Cholesterol sulfate, which is present in the skin, is a cause of sterile inflammation through agonizing Mincle signalling.[7] The protein SAP130 signal through Mincle.[8] Beta-glucosylceramide, which accumulates as a result of the lysosomal storage disorder Gaucher’s disease, signals through Mincle.[9]

Mincle agonists from microbes

Mycobacteria and corynebacteria produce a wide range of glycolipids that can signal through Mincle. These include glucose and trehalose mycolates, and their closely related corynomycolates from mycobacteria and corynebacteria.[10] Glycosyl diglycerides from various pathogenic and commensal bacteria and fungi such as Lactobacillus plantarum,[11] Streptococcus pneumoniae,[12][13] Mycobacterium tuberculosis[14] and Malassezia sp.[15]

See also

References

  1. ↑ Moody, DB; Matsunaga, I (2009). "Mincle is a long sought receptor for mycobacterial cord factor". Journal of Experimental Medicine. 206 (13): 2879–88. doi:10.1084/jem.20092533. PMC 2806465. PMID 20008525.
  2. ↑ 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". Journal of Experimental Medicine. 206 (13): 2865–8. doi:10.1084/jem.20091750. PMC 2806462. PMID 20008526.
  3. ↑ Miyake, Y; Toyonaga K; Mori D; Kakuta S; Hoshino Y; Oyamada A; Yamada H; Ono K; Suyama M; Iwakura Y; Yoshikai Y; Yamasaki S (2013). "C-type lectin MCL is an FcRγ-coupled receptor that mediates the adjuvanticity of mycobacterial cord factor". Immunity. 38 (5): 1050–1062. doi:10.1016/j.immuni.2013.03.010. PMID 23602766.
  4. ↑ Richardson, Mark B.; Williams, Spencer J. (2014-06-23). "MCL and Mincle: C-Type Lectin Receptors That Sense Damaged Self and Pathogen-Associated Molecular Patterns". Frontiers in Immunology. 5: 288. doi:10.3389/fimmu.2014.00288. ISSN 1664-3224. PMC 4066366. PMID 25002863.
  5. ↑ Strasser D, Neumann K, Bergmann H, Marakalala MJ, Guler R, Rojowska A; et al. (2012). "Syk kinase-coupled C-type lectin receptors engage protein kinase C-δ to elicit Card9 adaptor-mediated innate immunity". Immunity. 36 (1): 32–42. doi:10.1016/j.immuni.2011.11.015. PMC 3477316. PMID 22265677.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  6. ↑ Kiyotake, R; Oh-Hora, M; Ishikawa, E; Miyamoto, T; Ishibashi, T; Yamasaki, S (16 October 2015). "Human Mincle Binds to Cholesterol Crystals and Triggers Innate Immune Responses". The Journal of Biological Chemistry. 290 (42): 25322–32. doi:10.1074/jbc.M115.645234. PMC 4646182. PMID 26296894.
  7. ↑ Kostarnoy, AV; Gancheva, PG; Lepenies, B; Tukhvatulin, AI; Dzharullaeva, AS; Polyakov, NB; Grumov, DA; Egorova, DA; Kulibin, AY; Bobrov, MA; Malolina, EA; Zykin, PA; Soloviev, AI; Riabenko, E; Maltseva, DV; Sakharov, DA; Tonevitsky, AG; Verkhovskaya, LV; Logunov, DY; Naroditsky, BS; Gintsburg, AL (28 March 2017). "Receptor Mincle promotes skin allergies and is capable of recognizing cholesterol sulfate". Proceedings of the National Academy of Sciences of the United States of America. 114 (13): E2758–E2765. Bibcode:2017PNAS..114E2758K. doi:10.1073/pnas.1611665114. PMC 5380039. PMID 28292894.
  8. ↑ Yamasaki, S; Ishikawa, E; Sakuma, M; Hara, H; Ogata, K; Saito, T (October 2008). "Mincle is an ITAM-coupled activating receptor that senses damaged cells". Nature Immunology. 9 (10): 1179–88. doi:10.1038/ni.1651. PMID 18776906. S2CID 205361789.
  9. ↑ Nagata, Masahiro; Izumi, Yoshihiro; Ishikawa, Eri; Kiyotake, Ryoko; Doi, Rieko; Iwai, Satoru; Omahdi, Zakaria; Yamaji, Toshiyuki; Miyamoto, Tomofumi (18 April 2017). "Intracellular metabolite β-glucosylceramide is an endogenous Mincle ligand possessing immunostimulatory activity". Proceedings of the National Academy of Sciences of the United States of America. 114 (16): E3285–E3294. Bibcode:2017PNAS..114E3285N. doi:10.1073/pnas.1618133114. ISSN 1091-6490. PMC 5402399. PMID 28373578.
  10. ↑ van der Peet, PL; Gunawan, C; Torigoe, S; Yamasaki, S; Williams, Spencer J (2015). "Corynomycolic acid-containing glycolipids signal through the pattern recognition receptor Mincle". Chem. Commun. 51 (24): 5100–5103. doi:10.1039/c5cc00085h. PMID 25714652.
  11. ↑ Shah, S; Nagata M; Yamasaki D; Williams SJ (2016). "Total synthesis of a cyclopropane-fatty acid α-glucosyl diglyceride from Lactobacillus plantarum and identification of its ability to signal through Mincle". Chemical Communications. 52 (72): 10902–1065. doi:10.1039/C6CC05631H. PMID 27533919.
  12. ↑ Behler-Janbeck, F; Takano, T; Maus, R; Stolper, J; Jonigk, D; Tort Tarrés, M; Fuehner, T; Prasse, A; Welte, T; Timmer, MS; Stocker, BL; Nakanishi, Y; Miyamoto, T; Yamasaki, S; Maus, UA (December 2016). "C-type Lectin Mincle Recognizes Glucosyl-diacylglycerol of Streptococcus pneumoniae and Plays a Protective Role in Pneumococcal Pneumonia". PLOS Pathogens. 12 (12): e1006038. doi:10.1371/journal.ppat.1006038. PMC 5140071. PMID 27923071.
  13. ↑ Imai, T; Matsumura, T; Mayer-Lambertz, S; Wells, CA; Ishikawa, E; Butcher, SK; Barnett, TC; Walker, MJ; Imamura, A; Ishida, H; Ikebe, T; Miyamoto, T; Ato, M; Ohga, S; Lepenies, B; van Sorge, NM; Yamasaki, S (6 November 2018). "Lipoteichoic acid anchor triggers Mincle to drive protective immunity against invasive group A Streptococcus infection". Proceedings of the National Academy of Sciences of the United States of America. 115 (45): E10662–E10671. Bibcode:2018PNAS..11510662I. doi:10.1073/pnas.1809100115. PMC 6233082. PMID 30352847.
  14. ↑ Richardson MB, S, S, SJ., MB; Torigoe, S; Yamasaki, S; Williams, SJ (2015). "Mycobacterium tuberculosis β-gentiobiosyl diacylglycerides signal through the pattern recognition receptor Mincle: total synthesis and structure activity relationships". Chem. Commun. 51 (81): 15027–30. doi:10.1039/c5cc04773k. PMID 26310657.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  15. ↑ Ishikawa, T; Itoh, F; Yoshida, S; Saijo, S; Matsuzawa, T; Gonoi, T; Saito, T; Okawa, Y; Shibata, N; Miyamoto, T; Yamasaki, S (17 April 2013). "Identification of distinct ligands for the C-type lectin receptors Mincle and Dectin-2 in the pathogenic fungus Malassezia". Cell Host & Microbe. 13 (4): 477–88. doi:10.1016/j.chom.2013.03.008. PMID 23601109.


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