结核分枝杆菌脂阿拉伯甘露聚糖的免疫调节作用和诊断价值

doi:10.3969/j.issn.1000-6621.2021.08.018

摘要/Abstract

摘要：

结核分枝杆菌具有富含脂质的细胞壁,这种结构有助于结核分枝杆菌维持自身毒力并长期潜伏于宿主体内。脂阿拉伯甘露聚糖是结核分枝杆菌细胞壁中的重要组分,其复杂和独特的结构对结核分枝杆菌的生长、生存和毒力至关重要。作者综述了脂阿拉伯甘露聚糖的结构、生物合成途径、在免疫反应中的作用及在结核病诊断中的应用价值,为其可能作为一种新的结核病诊断生物标志物提供新的视野与思路。

关键词: 甘露聚糖类, 分枝杆菌,结核, 免疫, 诊断

Abstract:

Mycobacterium tuberculosis (MTB) cell wall contains rich lipids, which helps to maintain its own virulence and the long-term latent in the host. Lipoarabinomannan (LAM) is an important component in the cell wall of MTB, and its complex and unique structure is crucial for the growth, survival and virulence of MTB. In this review, we summarized the structure, biosynthetic pathway of LAM and its role in immune response as well as its application value in tuberculosis diagnosis. It could provide a new vision and ideas for its potential as a new biomarker for tuberculosis diagnosis.

Key words: Mannans, Mycobacterium tuberculosis, Immunity, Diagnosis

范雨鑫, 刘玫肖, 陈晶晶, 徐鑫, 张宇, 岳鹏, 曹文静, 宝福凯, 柳爱华. 结核分枝杆菌脂阿拉伯甘露聚糖的免疫调节作用和诊断价值[J]. 中国防痨杂志, 2021, 43(8): 847-852. doi: 10.3969/j.issn.1000-6621.2021.08.018

FAN Yu-xin, LIU Mei-xiao, CHEN Jing-jing, XU Xin, ZHANG Yu, YUE Peng, CAO Wen-jing, BAO Fu-kai, LIU Ai-hua. Immunomodulatory effect of Mycobacterium tuberculosis lipoarabinomannan and its value on tuberculosis diagnosis[J]. Chinese Journal of Antituberculosis, 2021, 43(8): 847-852. doi: 10.3969/j.issn.1000-6621.2021.08.018

图/表 2

参考文献 56

[1]	Jankute M, Grover S, Birch HL, et al. Genetics of Mycobacterial Arabinogalactan and Lipoarabinomannan Assembly. Microbiol Spectr, 2014, 2(4): MGM2-0013-2013. doi: 10.1128/microbiolspec.MGM2-0013-2013.
[2]	Misaki A, Azuma I, Yamamura Y. Structural and immunochemical studies on D-arabino-D-mannans and D-mannans of Mycobacterium tuberculosis and other Mycobacterium species. J Biochem, 1977, 82(6):1759-1770. doi: 10.1093/oxfordjournals.jbchem.a131874. URL pmid: 413830
[3]	Rahlwes KC, Puffal J, Morita YS. Purification and Analysis of Mycobacterial Phosphatidylinositol Mannosides, Lipomannan, and Lipoarabinomannan. Methods Mol Biol, 2019, 1954:59-75. doi: 10.1007/978-1-4939-9154-9_6.
[4]	Fukuda T, Matsumura T, Ato M, et al. Critical roles for lipomannan and lipoarabinomannan in cell wall integrity of mycobacteria and pathogenesis of tuberculosis. mBio, 2013, 4(1):e00472-12. doi: 10.1128/mBio.00472-12.
[5]	Mishra AK, Driessen NN, Appelmelk BJ, et al. Lipoarabinomannan and related glycoconjugates: structure, biogenesis and role in Mycobacterium tuberculosis physiology and host-pathogen interaction. FEMS Microbiol Rev, 2011, 35(6):1126-1157. doi: 10.1111/j.1574-6976.2011.00276.x. doi: 10.1111/j.1574-6976.2011.00276.x URL pmid: 21521247
[6]	Belcher Dufrisne M, Jorge CD, Timóteo CG, et al. Structural and Functional Characterization of Phosphatidylinositol-Phosphate Biosynthesis in Mycobacteria. J Mol Biol, 2020, 432(18):5137-5151. doi: 10.1016/j.jmb.2020.04.028. doi: S0022-2836(20)30330-2 URL pmid: 32389689
[7]	Kaur D, Obregón-Henao A, Pham H, et al. Lipoarabinomannan of Mycobacterium: mannose capping by a multifunctional terminal mannosyltransferase. Proc Natl Acad Sci U S A, 2008, 105(46):17973-17977. doi: 10.1073/pnas.0807761105. doi: 10.1073/pnas.0807761105 URL
[8]	Birch HL, Alderwick LJ, Appelmelk BJ, et al. A truncated lipoglycan from mycobacteria with altered immunological pro-perties. Proc Natl Acad Sci U S A, 2010, 107(6):2634-2639. doi: 10.1073/pnas.0915082107. doi: 10.1073/pnas.0915082107 URL
[9]	Jankute M, Alderwick LJ, Noack S, et al. Disruption of Mycobacterial AftB Results in Complete Loss of Terminal β(1→2) Arabinofuranose Residues of Lipoarabinomannan. ACS Chem Biol, 2017, 12(1):183-190. doi: 10.1021/acschembio.6b00898. doi: 10.1021/acschembio.6b00898 URL pmid: 28033704
[10]	Correia-Neves M, Fröberg G, Korshun L, et al. Biomarkers for tuberculosis: the case for lipoarabinomannan. ERJ Open Res, 2019, 5(1):00115-2018. doi: 10.1183/23120541.00115-2018.
[11]	Khoo KH, Dell A, Morris HR, et al. Inositol phosphate capping of the nonreducing termini of lipoarabinomannan from rapidly growing strains of Mycobacterium. J Biol Chem, 1995, 270(21):12380-12389. doi: 10.1074/jbc.270.21.12380. URL pmid: 7759478
[12]	Liu CH, Liu H, Ge B. Innate immunity in tuberculosis: host defense vs pathogen evasion. Cell Mol Immunol, 2017, 14(12):963-975. doi: 10.1038/cmi.2017.88. doi: 10.1038/cmi.2017.88 URL
[13]	Kang SS, Sim JR, Yun CH, et al. Lipoteichoic acids as a major virulence factor causing inflammatory responses via Toll-like receptor 2. Arch Pharm Res, 2016, 39(11):1519-1529. doi: 10.1007/s12272-016-0804-y. doi: 10.1007/s12272-016-0804-y URL
[14]	Turner J, Torrelles JB. Mannose-capped lipoarabinomannan in Mycobacterium tuberculosis pathogenesis. Pathog Dis, 2018, 76(4): fty026. doi: 10.1093/femspd/fty026.
[15]	Källenius G, Correia-Neves M, Buteme H, et al. Lipoarabinomannan, and its related glycolipids, induce divergent and opposing immune responses to Mycobacterium tuberculosis depending on structural diversity and experimental variations. Tuberculosis (Edinb), 2016, 96:120-130. doi: 10.1016/j.tube.2015.09.005. doi: 10.1016/j.tube.2015.09.005 URL
[16]	Zhou KL, Li X, Zhang XL, et al. Mycobacterial mannose-capped lipoarabinomannan: a modulator bridging innate and adaptive immunity. Emerg Microbes Infect, 2019, 8(1):1168-1177. doi: 10.1080/22221751.2019.1649097. doi: 10.1080/22221751.2019.1649097 URL
[17]	Lin PL, Flynn JL. CD8 T cells and Mycobacterium tuberculosis infection. Semin Immunopathol, 2015, 37(3):239-249. doi: 10.1007/s00281-015-0490-8. doi: 10.1007/s00281-015-0490-8 URL
[18]	Kallert S, Zenk SF, Walther P, et al. Liposomal delivery of lipoarabinomannan triggers Mycobacterium tuberculosis specific T-cells. Tuberculosis (Edinb), 2015, 95(4):452-462. doi: 10.1016/j.tube.2015.04.001. doi: 10.1016/j.tube.2015.04.001 URL
[19]	Van Rhijn I, Moody DB. CD1 and mycobacterial lipids activate human T cells. Immunol Rev, 2015, 264(1):138-153. doi: 10.1111/imr.12253. doi: 10.1111/imr.2015.264.issue-1 URL
[20]	Chancellor A, Tocheva AS, Cave-Ayland C, et al. CD1b-restricted GEM T cell responses are modulated by Mycobacterium tuberculosis mycolic acid meromycolate chains. Proc Natl Acad Sci U S A, 2017, 114(51):E10956-E10964. doi: 10.1073/pnas.1708252114. doi: 10.1073/pnas.1708252114 URL
[21]	Correia-Neves M, Sundling C, Cooper A, et al. Lipoarabinomannan in Active and Passive Protection Against Tuberculosis. Front Immunol, 2019, 10:1968. doi: 10.3389/fimmu.2019.01968. doi: 10.3389/fimmu.2019.01968 URL pmid: 31572351
[22]	Busch M, Herzmann C, Kallert S, et al. Lipoarabinomannan-Responsive Polycytotoxic T Cells Are Associated with Protection in Human Tuberculosis. Am J Respir Crit Care Med, 2016, 194:345-355. doi: 10.1164/rccm.201509-1746OC. doi: 10.1164/rccm.201509-1746OC URL
[23]	Jacobs AJ, Mongkolsapaya J, Screaton GR, et al. Antibodies and tuberculosis. Tuberculosis (Edinb), 2016, 101:102-113. doi: 10.1016/j.tube.2016.08.001. doi: 10.1016/j.tube.2016.08.001 URL
[24]	Valentini D, Rao M, Ferrara G, et al. Immune recognition surface construction of Mycobacterium tuberculosis epitope-specific antibody responses in tuberculosis patients identified by peptide microarrays. Int J Infect Dis, 2017, 56:155-166. doi: 10.1016/j.ijid.2017.01.015. doi: S1201-9712(17)30018-8 URL pmid: 28192214
[25]	Beatty WL, Rhoades ER, Ullrich HJ, et al. Trafficking and release of mycobacterial lipids from infected macrophages. Traffic, 2000, 1(3):235-247. doi: 10.1034/j.1600-0854.2000.010306.x. URL pmid: 11208107
[26]	Mahon RN, Sande OJ, Rojas RE, et al. Mycobacterium tuberculosis ManLAM inhibits T-cell-receptor signaling by interfe-rence with ZAP-70, Lck and LAT phosphorylation. Cell Immunol, 2012, 275(1/2):98-105. doi: 10.1016/j.cellimm.2012.02.009. doi: 10.1016/j.cellimm.2012.02.009 URL
[27]	Wong EA, Evans S, Kraus CR, et al. IL-10 Impairs Local Immune Response in Lung Granulomas and Lymph Nodes during Early Mycobacterium tuberculosis Infection. J Immunol, 2020, 204(3):644-659. doi: 10.4049/jimmunol.1901211. doi: 10.4049/jimmunol.1901211 URL
[28]	Schaible UE, Winau F, Sieling PA, et al. Apoptosis facilitates antigen presentation to T lymphocytes through MHC-I and CD1 in tuberculosis. Nat Med, 2003, 9(8):1039-1046. doi: 10.1038/nm906. URL pmid: 12872166
[29]	王连波, 章志华, 刘丰胜, 等. GeneXpert MTB/RIF在膝关节结核诊断及利福平耐药检测中的应用价值. 结核与肺部疾病杂志, 2021, 2(1):23-25. doi: 10.3969/j.issn.2096-8493.2021.01.006.
[30]	England K, Masini T, Fajardo E. Detecting tuberculosis: rapid tools but slow progress. Public Health Action, 2019, 9(3):80-83. doi: 10.5588/pha.19.0013. doi: 10.5588/pha.19.0013 URL pmid: 31803577
[31]	何翼君, 张浩然, 辛赫男, 等. 结核菌素皮肤试验的应用及其优化. 中国防痨杂志, 2021, 43(3):204-210. doi: 10.3969/j.issn.1000-6621.2021.03.003.
[32]	Barth RE, Mudrikova T, Hoepelman AI. Interferon-gamma release assays (IGRAs) in high-endemic settings: could they play a role in optimizing global TB diagnostics? Evaluating the possibilities of using IGRAs to diagnose active TB in a rural African setting. Int J Infect Dis, 2008, 12(6):e1-6. doi: 10.1016/j.ijid.2008.03.026.
[33]	Bastian I, Coulter C, National Tuberculosis Advisory Committee (NTAC). Position statement on interferon-gamma release assays for the detection of latent tuberculosis infection. Commun Dis Intell Q Rep, 2017, 41(4):E322-E336.
[34]	Sada E, Brennan PJ, Herrera T, et al. Evaluation of lipoarabinomannan for the serological diagnosis of tuberculosis. J Clin Microbiol, 1990, 28(12):2587-2590. doi: 10.1128/jcm.28.12.2587-2590.1990. URL pmid: 2126265
[35]	Salgame P, Geadas C, Collins L, et al. Latent tuberculosis infection-Revisiting and revising concepts. Tuberculosis (Edinb), 2015, 95(4):373-384. doi: 10.1016/j.tube.2015.04.003. doi: 10.1016/j.tube.2015.04.003 URL
[36]	Drain PK, Gounder L, Grobler A, et al. Urine lipoarabinomannan to monitor antituberculosis therapy response and predict mortality in an HIV-endemic region: a prospective cohort study. BMJ Open, 2015, 5(4):e006833. doi: 10.1136/bmjopen-2014-006833. doi: 10.1136/bmjopen-2014-006833 URL
[37]	Kroidl I, Clowes P, Reither K, et al. Performance of urine lipoarabinomannan assays for paediatric tuberculosis in Tanzania. Eur Respir J, 2015, 46(3):761-770. doi: 10.1183/09031936.00003315. doi: 10.1183/09031936.00003315 URL
[38]	Bahr NC, Tugume L, Boulware DR. A Word of Caution in Considering the Use of the Lipoarabinomannan Lateral Flow Assay on Cerebrospinal Fluid for Detection of Tuberculous Meningitis. J Clin Microbiol, 2016, 54(1):241-242. doi: 10.1128/JCM.02753-15. doi: 10.1128/JCM.02753-15 URL
[39]	Dheda K, Davids V, Lenders L, et al. Clinical utility of a commercial LAM-ELISA assay for TB diagnosis in HIV-infected patients using urine and sputum samples. PLoS One, 2010, 5(3):e9848. doi: 10.1371/journal.pone.0009848. doi: 10.1371/journal.pone.0009848 URL
[40]	Nakiyingi L, Moodley VM, Manabe YC, et al. Diagnostic accuracy of a rapid urine lipoarabinomannan test for tuberculosis in HIV-infected adults. J Acquir Immune Defic Syndr, 2014, 66(3):270-279. doi: 10.1097/QAI.0000000000000151. doi: 10.1097/QAI.0000000000000151 URL pmid: 24675585
[41]	Lawn SD. Point-of-care detection of lipoarabinomannan (LAM) in urine for diagnosis of HIV-associated tuberculosis: a state of the art review. BMC Infect Dis, 2012, 12:103. doi: 10.1186/1471-2334-12-103. doi: 10.1186/1471-2334-12-103 URL
[42]	Boehme CC, Nabeta P, Hillemann D, et al. Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med, 2010, 363(11):1005-1015. doi: 10.1056/NEJMoa0907847. doi: 10.1056/NEJMoa0907847 URL
[43]	Nakiyingi L, Ssengooba W, Nakanjako D, et al. Predictors and outcomes of mycobacteremia among HIV-infected smear-negative presumptive tuberculosis patients in Uganda. BMC Infect Dis, 2015, 15:62. doi: 10.1186/s12879-015-0812-4. doi: 10.1186/s12879-015-0812-4 URL pmid: 25888317
[44]	Shah M, Hanrahan C, Wang ZY, et al. Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in HIV-positive adults. Cochrane Database Syst Rev, 2016, 2016(5):CD011420. doi: 10.1002/14651858.CD011420.
[45]	Doublier S, Zennaro C, Spatola T, et al. HIV-1 Tat reduces nephrin in human podocytes: a potential mechanism for enhanced glomerular permeability in HIV-associated nephropathy. AIDS, 2007, 21(4):423-432. doi: 10.1097/QAD.0b013e328012c522. URL pmid: 17301560
[46]	Sahle SN, Asress DT, Tullu KD, et al. Performance of point-of-care urine test in diagnosing tuberculosis suspects with and without HIV infection in selected peripheral health settings of Addis Ababa, Ethiopia. BMC Res Notes, 2017, 10(1):74. doi: 10.1186/s13104-017-2404-4. doi: 10.1186/s13104-017-2404-4 URL
[47]	Suwanpimolkul G, Kawkitinarong K, Manosuthi W, et al. Utility of urine lipoarabinomannan (LAM) in diagnosing tuberculosis and predicting mortality with and without HIV: prospective TB cohort from the Thailand Big City TB Research Network. Int J Infect Dis, 2017, 59:96-102. doi: 10.1016/j.ijid.2017.04.017. doi: S1201-9712(17)30129-7 URL pmid: 28457751
[48]	De P, Shi L, Boot C, et al. Comparative Structural Study of Terminal Ends of Lipoarabinomannan from Mice Infected Lung Tissues and Urine of a Tuberculosis Positive Patient. ACS Infect Dis, 2020, 6(2):291-301. doi: 10.1021/acsinfecdis.9b00355. doi: 10.1021/acsinfecdis.9b00355 URL
[49]	Flores J, Cancino JC, Chavez-Galan L. Lipoarabinomannan as a Point-of-Care Assay for Diagnosis of Tuberculosis: How Far Are We to Use It? Front Microbiol, 2021, 12:638047. doi: 10.3389/fmicb.2021.638047. doi: 10.3389/fmicb.2021.638047 URL
[50]	Jakhar S, Sakamuri R, Vu D, et al. Interaction of amphiphilic lipoarabinomannan with host carrier lipoproteins in tuberculosis patients: Implications for blood-based diagnostics. PLoS One, 2021, 16(4):e0243337. doi: 10.1371/journal.pone.0243337. doi: 10.1371/journal.pone.0243337 URL
[51]	Quinn CM, Kagimu E, Okirworth M, et al. Fujifilm SILVAMP TB LAM assay on cerebrospinal fluid for the detection of tuberculous meningitis in HIV-infected adults. Clin Infect Dis, 2021, 3:ciaa1910. doi: 10.1093/cid/ciaa1910.
[52]	Broger T, Nicol MP, Székely R, et al. Diagnostic accuracy of a novel tuberculosis point-of-care urine lipoarabinomannan assay for people living with HIV: A meta-analysis of individual in- and outpatient data. PLoS Med, 2020, 17(5):e1003113. doi: 10.1371/journal.pmed.1003113. doi: 10.1371/journal.pmed.1003113 URL
[53]	Sakamuri RM, Price DN, Lee M, et al. Association of lipoarabinomannan with high density lipoprotein in blood: implications for diagnostics. Tuberculosis (Edinb), 2013, 93(3):301-307. doi: 10.1016/j.tube.2013.02.015. doi: 10.1016/j.tube.2013.02.015 URL
[54]	Levay A, Brenneman R, Hoinka J, et al. Identifying high-affinity aptamer ligands with defined cross-reactivity using high-throughput guided systematic evolution of ligands by exponential enrichment. Nucleic Acids Res, 2015, 43(12):e82. doi: 10.1093/nar/gkv534. doi: 10.1093/nar/gkv534 URL
[55]	Zhou Y, Xiong H, Chen R, et al. Aptamer Detection of Mycobaterium tuberculosis Mannose-Capped Lipoarabinomannan in Lesion Tissues for Tuberculosis Diagnosis. Front Cell Infect Microbiol, 2021, 11:634915. doi: 10.3389/fcimb.2021.634915. doi: 10.3389/fcimb.2021.634915 URL
[56]	Tortoli E, Russo C, Piersimoni C, et al. Clinical validation of Xpert MTB/RIF for the diagnosis of extrapulmonary tuberculosis. Eur Respir J, 2012, 40(2):442-447. doi: 10.1183/09031936.00176311. doi: 10.1183/09031936.00176311 URL