味觉受体信号转导机制及对微生物的调控

doi:10.7518/hxkq.2017.05.020

摘要/Abstract

摘要：

口腔味蕾细胞中的味觉受体有助于机体鉴别营养物质和有害物质,对哺乳动物的生存具有重要意义。近年来发现,味觉受体及其下游信号转导通路还在呼吸道、大脑、胃肠道等多种组织细胞中表达。表达味觉受体的细胞统称为化学感官细胞,在抵抗微生物感染、调节营养吸收、维持内环境稳态中发挥重要作用。目前已发现多种组织细胞中的味觉受体可识别细菌等微生物,介导宿主免疫应答反应,在感染性疾病发生发展过程中起到重要作用。本文就味觉受体的信号转导机制及其对微生物的调控作用进行综述。

关键词: 味觉受体, 微生物, 化学感官细胞, 固有免疫

Abstract:

Taste receptors guide individuals to consume nutrients while avoiding potentially noxious substances. Interes-tingly, recent studies have shown that taste receptors are also expressed beyond the taste buds, including brain, respiratory system, and digestive system, etc. These extragustatory taste receptors play important roles in microbial infection, nutrient uptake and host homeostasis. Mang extragustatory taste receptors have been proposed to sense microorganisms and regulate host innate defense. More importantly, polymorphisms of genes encoding taste receptor, particularly bitter taste receptor, are linked to different innate defensive responses. This review introduces the molecular basis of taste signal transduction, and the role of taste receptors in the regulation of innate immunity during microbial infection were further discussed in detail.

Key words: taste receptor, microorganisms, chemosensory cells, innate immunity

中图分类号:

陆洋宇, 席苒珲, 郑欣, 何金枝, 徐欣. 味觉受体信号转导机制及对微生物的调控[J]. 华西口腔医学杂志, 2017, 35(5): 549-554.

Yangyu Lu, Ranhui Xi, Xin Zheng, Jinzhi He, Xin Xu. Taste signal transduction and the role of taste receptors in the regulation of microbial infection[J]. West China Journal of Stomatology, 2017, 35(5): 549-554.

参考文献 50

[1]	Chandrashekar J, Hoon MA, Ryba NJP, et al.The receptors and cells for mammalian taste[J]. Nature, 2006, 444(7117):288-294.
[2]	Lee RJ, Cohen NA.Taste receptors in innate immunity[J]. Cell Mol Life Sci, 2015, 72(2):217-236.
[3]	Laffitte A, Neiers F, Briand L.Functional roles of the sweet taste receptor in oral and extraoral tissues[J]. Curr Opin Clin Nutr Metab Care, 2014,17(4):379-385.
[4]	Li F.Taste perception: from the tongue to the testis[J]. Mol Hum Reprod, 2013, 19(6):349-360.
[5]	Adler E, Hoon MA, Mueller KL, et al.A novel family of mammalian taste receptors[J]. Cell, 2000, 100(6):693-702.
[6]	Barlow LA.Progress and renewal in gustation: new insights into taste bud development[J]. Development, 2015, 142(21):3620-3629.
[7]	Iwata S, Yoshida R, Ninomiya Y.Taste transductions in taste receptor cells: basic tastes and moreover[J]. Curr Pharm Des, 2014, 20(16):2684-2692.
[8]	Ye W, Chang RB, Bushman JD, et al.The K+ channel KIR2.1 functions in tandem with proton influx to mediate sour taste transduction[J]. Proc Natl Acad Sci U S A, 2016, 113(2):E229-E238.
[9]	Chandrashekar J, Mueller KL, Hoon MA, et al.T2Rs func-tion as bitter taste receptors[J]. Cell, 2000, 100(6):703-711.
[10]	Shi P, Zhang J, Yang H, et al.Adaptive diversification of bitter taste receptor genes in mammalian evolution[J]. Mol Biol Evol, 2003, 20(5):805-814.
[11]	Shi P, Zhang J.Contrasting modes of evolution between vertebrate sweet/umami receptor genes and bitter receptor genes[J]. Mol Biol Evol, 2006, 23(2):292-300.
[12]	Jaggupilli A, Howard R, Upadhyaya JD, et al.Bitter taste receptors: novel insights into the biochemistry and pharma-cology[J]. Int J Biochem Cell Biol, 2016, 77(Pt B):184-196.
[13]	Pydi SP, Sobotkiewicz T, Billakanti R, et al.Amino acid derivatives as bitter taste receptor (T2R) blockers[J]. J Biol Chem, 2014, 289(36):25054-25066.
[14]	Bufe B, Breslin PA, Kuhn C, et al.The molecular basis of individual differences in phenylthiocarbamide and propyl-thiouracil bitterness perception[J]. Curr Biol, 2005, 15(4):322-327.
[15]	Kim UK, Jorgenson E, Coon H, et al.Positional cloning of the human quantitative trait locus underlying taste sensiti-vity to phenylthiocarbamide[J]. Science, 2003, 299(5610):1221-1225.
[16]	Tan J, Abrol R, Trzaskowski B, et al.3D structure predic-tion of TAS2R38 bitter receptors bound to agonists phenyl-thiocarbamide (PTC) and 6-n-propylthiouracil (PROP)[J]. J Chem Inf Model, 2012, 52(7):1875-1885.
[17]	Guo SW, Reed DR.The genetics of phenylthiocarbamide perception[J]. Ann Hum Biol, 2001, 28(2):111-142.
[18]	Zhao GQ, Zhang Y, Hoon MA, et al.The receptors for mam-malian sweet and umami taste[J]. Cell, 2003, 115(3):255-266.
[19]	Sukumaran SK, Yee KK, Iwata S, et al.Taste cell-expressed α-glucosidase enzymes contribute to gustatory responses to disaccharides[J]. Proc Natl Acad Sci U S A, 2016, 113(21):6035-6040.
[20]	Yee KK, Sukumaran SK, Kotha R, et al.Glucose transpor-ters and ATP-gated K+ (KATP) metabolic sensors are pre-sent in type 1 taste receptor 3 (T1r3)-expressing taste cells[J]. Proc Natl Acad Sci U S A, 2011, 108(13):5431-5436.
[21]	Treesukosol Y, Smith KR, Spector AC.The functional role of the T1R family of receptors in sweet taste and feeding[J]. Physiol Behav, 2011, 105(1):14-26.
[22]	Pal Choudhuri S, Delay RJ, Delay ER.L-Amino acids elicit diverse response patterns in taste sensory cells: a role for multiple receptors[J]. PloS One, 2015, 10(6):e0130088.
[23]	Temussi PA.Sweet, bitter and umami receptors: a complex relationship[J]. Trends Biochem Sci, 2009, 34(6):296-302.
[24]	Chaudhari N, Roper SD.The cell biology of taste[J]. J Cell Biol, 2010, 190(3):285-296.
[25]	Douglas JE, Saunders CJ, Reed DR, et al.A role for airway taste receptor modulation in the treatment of upper respira-tory infections[J]. Expert Rev Respir Med, 2016, 10(2):157-170.
[26]	Roper SD.Taste buds as peripheral chemosensory processors[J]. Semin Cell Dev Biol, 2013, 24(1):71-79.
[27]	Tizzano M, Gulbransen BD, Vandenbeuch A, et al.Nasal chemosensory cells use bitter taste signaling to detect irri-tants and bacterial signals[J]. Proc Natl Acad Sci U S A, 2010, 107(7):3210-3215.
[28]	Lee RJ, Xiong G, Kofonow JM, et al.T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection[J]. J Clin Invest, 2012, 122(11):4145-4159.
[29]	Lee RJ, Kofonow JM, Rosen PL, et al.Bitter and sweet taste receptors regulate human upper respiratory innate immunity[J]. J Clin Invest, 2014, 124(3):1393-1405.
[30]	Howitt MR, Lavoie S, Michaud M, et al.Tuft cells, taste-chemosensory cells, orchestrate parasite type 2 immunity in the gut[J]. Science, 2016, 351(6279):1329-1333.
[31]	Ricciardolo FL.Multiple roles of nitric oxide in the airways[J]. Thorax, 2003, 58(2):175-182.
[32]	Storm WL, Johnson JA, Worley BV, et al.Dual action anti-microbial surfaces via combined nitric oxide and silver release[J]. J Biomed Mater Res A, 2015, 103(6):1974-1984.
[33]	Maurer S, Wabnitz GH, Kahle NA, et al.Tasting Pseudo-monas aeruginosa biofilms: human neutrophils express the bitter receptor T2R38 as sensor for the quorum sensing mole-cule N-(3-oxododecanoyl)-l-homoserine lactone[J]. Front Immunol, 2015, 6:369.
[34]	Schwabe RF, Jobin C.The microbiome and cancer[J]. Nat Rev Cancer, 2013, 13(11):800-812.
[35]	Gaida MM, Mayer C, Dapunt U, et al.Expression of the bitter receptor T2R38 in pancreatic cancer: localization in lipid droplets and activation by a bacteria-derived quorum-sensing molecule[J]. Oncotarget, 2016, 7(11):12623-12632.
[36]	Adappa ND, Truesdale CM, Workman AD, et al.Correla-tion of T2R38 taste phenotype and in vitro biofilm forma-tion from nonpolypoid chronic rhinosinusitis patients[J]. Int Forum Allergy Rhiol, 2016, 6(8):783-791.
[37]	Adappa ND, Howland TJ, Palmer JN, et al.Genetics of the taste receptor T2R38 correlates with chronic rhinosinusitis necessitating surgical intervention[J]. Int Forum Allergy Rhiol, 2013, 3(3):184-187.
[38]	Adappa ND, Zhang Z, Palmer JN, et al.The bitter taste receptor T2R38 is an independent risk factor for chronic rhinosinusitis requiring sinus surgery[J]. Int Forum Allergy Rhiol, 2014, 4(1):3-7.
[39]	Adappa ND, Farquhar D, Palmer JN, et al.TAS2R38 geno-type predicts surgical outcome in nonpolypoid chronic rhi-nosinusitis[J]. Int Forum Allergy Rhiol, 2016, 6(1):25-33.
[40]	Gil S, Coldwell S, Drury JL, et al.Genotype-specific regu-lation of oral innate immunity by T2R38 taste receptor[J]. Mol Immunol, 2015, 68(2 Pt C):663-670.
[41]	Wendell S, Wang X, Brown M, et al.Taste genes associated with dental caries[J]. J Dent Res, 2010, 89(11):1198-1202.
[42]	Pezzulo AA, Gutierrez J, Duschner KS, et al.Glucose deple-tion in the airway surface liquid is essential for sterility of the airways[J]. PloS One, 2011, 6(1):e16166.
[43]	Gerbe F, Legraverend C, Jay P.The intestinal epithelium tuft cells: specification and function[J]. Cell Mol Life Sci, 2012, 69(17):2907-2917.
[44]	von Moltke J, Ji M, Liang HE, et al. Tuft-cell-derived IL-25 regulates an intestinal ILC2-epithelial response circuit[J]. Nature, 2016, 529(7585):221-225.
[45]	Benford H, Bolborea M, Pollatzek E, et al.A sweet taste receptor-dependent mechanism of glucosensing in hypotha-lamic tanycytes[J]. Glia, 2017, 65(5):773-789.
[46]	Singh N, Vrontakis M, Parkinson F, et al.Functional bitter taste receptors are expressed in brain cells[J]. Biochem Bio-phys Res Commun, 2011, 406(1):146-151.
[47]	Depoortere I.Taste receptors of the gut: emerging roles in health and disease[J]. Gut, 2014, 63(1):179-190.
[48]	Henquin JC.Do pancreatic β cells “taste” nutrients to secrete insulin[J]. Sci Signal, 2012, 5(239):pe36.
[49]	Elliott RA, Kapoor S, Tincello DG.Expression and distri-bution of the sweet taste receptor isoforms T1R2 and T1R3 in human and rat bladders[J]. J Urol, 2011, 186(6):2455-2462.
[50]	Wolfle U, Elsholz FA, Kersten A, et al.Expression and func-tional activity of the human bitter taste receptor TAS2R38 in human placental tissues and JEG-3 cells[J]. Molecules, 2016, 21(3):306.