中国寄生虫学与寄生虫病杂志 ›› 2023, Vol. 41 ›› Issue (5): 527-531.doi: 10.12140/j.issn.1000-7423.2023.05.001
收稿日期:
2023-01-14
修回日期:
2023-03-30
出版日期:
2023-10-30
发布日期:
2023-11-06
通讯作者:
*冯萌(1984-),男,博士,副教授,从事医学原虫免疫、致病机制、寄生虫转录组学与蛋白质组学等研究。 E-mail:作者简介:
薛羽珊(2002-),女,本科生,复旦大学基础医学(强基计划)专业。E-mail:20301010015@fudan.edu.cn
XUE Yushan1(), LIN Ping1,2, CHENG Xunjia1, FENG Meng1,*()
Received:
2023-01-14
Revised:
2023-03-30
Online:
2023-10-30
Published:
2023-11-06
Contact:
*E-mail: 摘要:
刚地弓形虫是一种在世界范围内广泛分布的专性细胞内寄生原虫,可引起人兽共患弓形虫病。脑内弓形虫感染可导致中枢神经系统病变,引起抑郁症、精神分裂症、癫痫等症状。本文就弓形虫通过血脑屏障建立慢性感染,引起中枢神经系统损伤和脑部疾病的机制进行综述。
中图分类号:
薛羽珊, 林萍, 程训佳, 冯萌. 慢性弓形虫感染对宿主中枢神经系统的损伤及其作用机制[J]. 中国寄生虫学与寄生虫病杂志, 2023, 41(5): 527-531.
XUE Yushan, LIN Ping, CHENG Xunjia, FENG Meng. Damage caused by chronic infection of Toxoplasma gondii on the host central nervous system and its mechanism[J]. Chinese Journal of Parasitology and Parasitic Diseases, 2023, 41(5): 527-531.
[1] |
Smith NC, Goulart C, Hayward JA, et al. Control of human toxoplasmosis[J]. Int J Parasitol, 2021, 51(2/3): 95-121.
doi: 10.1016/j.ijpara.2020.11.001 |
[2] |
Su YJ, Ma ZD, Qiao X, et al. Geospatial epidemiology of Toxoplasma gondii infection in livestock, pets, and humans in China, 1984—2020[J]. Parasitol Res, 2022, 121(2): 743-750.
doi: 10.1007/s00436-021-07415-1 |
[3] | Zhu XP, Su C. Human parasitology[M]. Beijing: People’s Medical Publishing House, 2018: 69-73. (in Chinese) |
(诸欣平, 苏川. 人体寄生虫学[M]. 北京: 人民卫生出版社, 2018: 69-73.) | |
[4] |
Lima TS, Lodoen MB. Mechanisms of human innate immune evasion by Toxoplasma gondii[J]. Front Cell Infect Microbiol, 2019, 9: 103.
doi: 10.3389/fcimb.2019.00103 |
[5] |
Zhao XY, Ewald SE. The molecular biology and immune control of chronic Toxoplasma gondii infection[J]. J Clin Invest, 2020, 130(7): 3370-3380.
doi: 10.1172/JCI136226 |
[6] | Han SQ, Wu K. Advances in the study of bradyzoite-associated proteins of Toxoplasma gondii[J]. Chin J Zoonoses, 2014, 30(9): 965-970. (in Chinese) |
(韩思琪, 吴焜. 弓形虫缓殖子期相关蛋白的研究进展[J]. 中国人兽共患病学报, 2014, 30(9): 965-970.) | |
[7] | Zheng WH, Dou NX, Lü ZY. Mechanism of psychiatric disorders caused by Toxoplasma gondii infection[J]. J Trop Med, 2017, 17(1): 119-122. (in Chinese) |
(郑维泓, 窦宁馨, 吕志跃. 弓形虫感染引起精神疾病的机制研究进展[J]. 热带医学杂志, 2017, 17(1): 119-122.) | |
[8] |
Lachenmaier SM, Deli MA, Meissner M, et al. Intracellular transport of Toxoplasma gondii through the blood-brain barrier[J]. J Neuroimmunol, 2011, 232(1/2): 119-130.
doi: 10.1016/j.jneuroim.2010.10.029 |
[9] |
Wohlfert EA, Blader IJ, Wilson EH. Brains and brawn: Toxoplasma infections of the central nervous system and skeletal muscle[J]. Trends Parasitol, 2017, 33(7): 519-531.
doi: 10.1016/j.pt.2017.04.001 |
[10] |
Kim H, Hong SH, Jeong HE, et al. Microfluidic model for in vitro acute Toxoplasma gondii infection and transendothelial migration[J]. Sci Rep, 2022, 12(1): 11449.
doi: 10.1038/s41598-022-15305-4 |
[11] |
Ortiz-Guerrero G, Gonzalez-Reyes RE, de-la-Torre A, et al. Pathophysiological mechanisms of cognitive impairment and neurodegeneration by Toxoplasma gondii infection[J]. Brain Sci, 2020, 10(6): 369.
doi: 10.3390/brainsci10060369 |
[12] |
Ma Y, Semba S, Khan RI, et al. Focal adhesion kinase regulates intestinal epithelial barrier function via redistribution of tight junction[J]. Biochim Biophys Acta, 2013, 1832(1): 151-159.
doi: 10.1016/j.bbadis.2012.10.006 pmid: 23064287 |
[13] |
Cook JH, Ueno N, Lodoen MB. Toxoplasma gondii disrupts β1 integrin signaling and focal adhesion formation during monocyte hypermotility[J]. J Biol Chem, 2018, 293(9): 3374-3385.
doi: 10.1074/jbc.M117.793281 |
[14] | Ross EC, Olivera GC, Barragan A. Dysregulation of focal adhesion kinase upon Toxoplasma gondii infection facilitates parasite translocation across polarised primary brain endothelial cell monolayers[J]. Cell Microbiol, 2019, 21(9): e13048. |
[15] |
Ross EC, Olivera GC, Barragan A. Early passage of Toxoplasma gondii across the blood-brain barrier[J]. Trends Parasitol, 2022, 38(6): 450-461.
doi: 10.1016/j.pt.2022.02.003 |
[16] |
Konradt C, Ueno N, Christian DA, et al. Endothelial cells are a replicative niche for entry of Toxoplasma gondii to the central nervous system[J]. Nat Microbiol, 2016, 1: 16001.
doi: 10.1038/nmicrobiol.2016.1 |
[17] |
Matta SK, Rinkenberger N, Dunay IR, et al. Toxoplasma gondii infection and its implications within the central nervous system[J]. Nat Rev Micro, 2021, 19(7): 467-480.
doi: 10.1038/s41579-021-00518-7 |
[18] |
Estato V, Stipursky J, Gomes F, et al. The neurotropic parasite Toxoplasma gondii induces sustained neuroinflammation with microvascular dysfunction in infected mice[J]. Am J Pathol, 2018, 188(11): 2674-2687.
doi: 10.1016/j.ajpath.2018.07.007 |
[19] |
Schneider CA, Figueroa Velez DX, Azevedo R, et al. Imaging the dynamic recruitment of monocytes to the blood-brain barrier and specific brain regions during Toxoplasma gondii infection[J]. Proc Natl Acad Sci USA, 2019, 116(49): 24796-24807.
doi: 10.1073/pnas.1915778116 |
[20] | Yang J, Yuan WY. Toxoplasma infection on nerve tissue damage and its mechanism through the blood-brain barrier[J]. Acta Neuro, 2019, 9(5): 40-43. (in Chinese) |
(杨靖, 苑文英. 弓形虫感染对神经组织损伤及通过血脑屏障机制[J]. 神经药理学报, 2019, 9(5): 40-43.) | |
[21] |
Hakimi MA, Olias P, Sibley LD. Toxoplasma effectors targeting host signaling and transcription[J]. Clin Microbiol Rev, 2017, 30(3): 615-645.
doi: 10.1128/CMR.00005-17 |
[22] |
Chen LF, Christian DA, Kochanowsky JA, et al. The Toxoplasma gondii virulence factor ROP16 acts in cis and trans, and suppresses T cell responses[J]. J Exp Med, 2020, 217(3): e20181757.
doi: 10.1084/jem.20181757 |
[23] |
Mercer HL, Snyder LM, Doherty CM, et al. Toxoplasma gondii dense granule protein GRA24 drives MyD88-independent p38 MAPK activation, IL-12 production and induction of protective immunity[J]. PLoS Pathog, 2020, 16(5): e1008572.
doi: 10.1371/journal.ppat.1008572 |
[24] |
Ólafsson EB, Barragan A. The unicellular eukaryotic parasite Toxoplasma gondii hijacks the migration machinery of mononuclear phagocytes to promote its dissemination[J]. Biol cell, 2020, 112(9): 239-250.
doi: 10.1111/boc.202000005 pmid: 32359185 |
[25] | Zhang YH, Wang L, Wang XL, et al. Microglial activation and inflammatory cytokine expression in the brain of chronic Toxoplasma gondii-infected mice[J]. Chin J Parasitol Parasit Dis, 2013, 31(3): 176-179, 184. (in Chinese) |
(张义华, 王璐, 汪学龙, 等. 慢性弓形虫感染小鼠小胶质细胞的活化与炎症因子的表达[J]. 中国寄生虫学与寄生虫病杂志, 2013, 31(3): 176-179, 184.) | |
[26] |
Schlüter D, Barragan A. Advances and challenges in understanding cerebral toxoplasmosis[J]. Front Immunol, 2019, 10: 242.
doi: 10.3389/fimmu.2019.00242 pmid: 30873157 |
[27] |
Suzuki Y. The immune system utilizes two distinct effector mechanisms of T cells depending on two different life cycle stages of a single pathogen, Toxoplasma gondii, to control its cerebral infection[J]. Parasitol Int, 2020, 76: 102030.
doi: 10.1016/j.parint.2019.102030 |
[28] |
Skariah S, McIntyre MK, Mordue DG. Toxoplasma gondii: determinants of tachyzoite to bradyzoite conversion[J]. Parasitol Res, 2010, 107(2): 253-260.
doi: 10.1007/s00436-010-1899-6 pmid: 20514494 |
[29] |
Augusto L, Wek RC, Jr Sullivan WJ. Host sensing and signal transduction during Toxoplasma stage conversion[J]. Mol Microbiol, 2021, 115(5): 839-848.
doi: 10.1111/mmi.v115.5 |
[30] |
Weiss LM, Dubey JP. Toxoplasmosis: a history of clinical observations[J]. Int J Parasitol, 2009, 39(8): 895-901.
doi: 10.1016/j.ijpara.2009.02.004 pmid: 19217908 |
[31] |
Wang T, Sun XH, Qin W, et al. From inflammatory reactions to neurotransmitter changes: implications for understanding the neurobehavioral changes in mice chronically infected with Toxoplasma gondii[J]. Behav Brain Res, 2019, 359: 737-748.
doi: 10.1016/j.bbr.2018.09.011 |
[32] | Alsaady I, Tedford E, Alsaad M, et al. Downregulation of the central noradrenergic system by Toxoplasma gondii infection[J]. Infect Immun, 2019, 87(2): e00789. |
[33] |
Yin K, Xu C, Zhao GH, et al. Epigenetic manipulation of psychiatric behavioral disorders induced by Toxoplasma gondii[J]. Front Cell Infect Microbiol, 2022, 12: 803502.
doi: 10.3389/fcimb.2022.803502 |
[34] |
Lang D, Schott BH, van Ham M, et al. Chronic Toxoplasma infection is associated with distinct alterations in the synaptic protein composition[J]. J Neuroinflammation, 2018, 15(1): 216.
doi: 10.1186/s12974-018-1242-1 |
[35] |
Ivashkiv LB. IFN-γ: signalling, epigenetics and roles in immunity, metabolism, disease and cancer immunotherapy[J]. Nat Rev Immunol, 2018, 18(9): 545-558.
doi: 10.1038/s41577-018-0029-z pmid: 29921905 |
[36] |
Vumma R, Johansson J, Venizelos N. Proinflammatory cytokines and oxidative stress decrease the transport of dopamine precursor tyrosine in human fibroblasts[J]. Neuropsychobiology, 2017, 75(4): 178-184.
doi: 10.1159/000485130 pmid: 29339668 |
[37] |
Birck C, Ginolhac A, Pavlou MAS, et al. NF-κB and TNF affect the astrocytic differentiation from neural stem cells[J]. Cells, 2021, 10(4): 840.
doi: 10.3390/cells10040840 |
[38] | Xing ME, Wang DW, Guo XG, et al. Update on the CD8+T cell immunity induced by Toxoplasma gondii infection in mice[J]. Heilongjiang Anim Sci Vet Med, 2017(13): 57-61. (in Chinese) |
(邢蒙恩, 王大为, 郭晓改, 等. 弓形虫感染引起小鼠体内CD8+T淋巴细胞免疫的研究[J]. 黑龙江畜牧兽医, 2017(13): 57-61.) | |
[39] |
Soleymani E, Faizi F, Heidarimoghadam R, et al. Association of T. gondii infection with suicide: a systematic review and meta-analysis[J]. BMC Public Health, 2020, 20(1): 766.
doi: 10.1186/s12889-020-08898-w pmid: 32448258 |
[40] |
Sadeghi M, Riahi SM, Mohammadi M, et al. An updated meta-analysis of the association between Toxoplasma gondii infection and risk of epilepsy[J]. Trans R Soc Trop Med Hyg, 2019, 113(8): 453-462.
doi: 10.1093/trstmh/trz025 |
[41] |
Nayeri T, Sarvi S, Moosazadeh M, et al. Relationship between toxoplasmosis and autism: a systematic review and meta-analysis[J]. Microb Pathog, 2020, 147: 104434.
doi: 10.1016/j.micpath.2020.104434 |
[42] |
Yalın Sapmaz Ş, Şen S, Özkan Y, et al. Relationship between Toxoplasma gondii seropositivity and depression in children and adolescents[J]. Psychiatry Res, 2019, 278: 263-267.
doi: 10.1016/j.psychres.2019.06.031 |
[43] |
Xiao JC, Prandovszky E, Kannan G, et al. Toxoplasma gondii: biological parameters of the connection to schizophrenia[J]. Schizophr Bull, 2018, 44(5): 983-992.
doi: 10.1093/schbul/sby082 pmid: 29889280 |
[44] |
Aisen PS, Cummings J, Jack CR Jr, et al. On the path to 2025: understanding the Alzheimer’s disease continuum[J]. Alzheimers Res Ther, 2017, 9(1): 60.
doi: 10.1186/s13195-017-0283-5 pmid: 28793924 |
[45] |
Torres L, Robinson SA, Kim DG, et al. Toxoplasma gondii alters NMDAR signaling and induces signs of Alzheimer’s disease in wild-type, C57BL/6 mice[J]. J Neuroinflammation, 2018, 15(1): 57.
doi: 10.1186/s12974-018-1086-8 |
[46] |
Jauhar S, Johnstone M, McKenna PJ. Schizophrenia[J]. Lancet, 2022, 399(10323): 473-486.
doi: 10.1016/S0140-6736(21)01730-X pmid: 35093231 |
[47] |
David CN, Frias ES, Szu JI, et al. GLT-1-dependent disruption of CNS glutamate homeostasis and neuronal function by the protozoan parasite Toxoplasma gondii[J]. PLoS Pathog, 2016, 12(6): e1005643.
doi: 10.1371/journal.ppat.1005643 |
[48] |
Yolken R, Torrey EF, Dickerson F. Evidence of increased exposure to Toxoplasma gondii in individuals with recent onset psychosis but not with established schizophrenia[J]. PLoS Negl Trop Dis, 2017, 11(11): e0006040.
doi: 10.1371/journal.pntd.0006040 |
[49] | Zhang C, Chen JT, Xin ZX, et al. Transcriptome analysis of mice brain chronically infected with Toxoplasma gondii and validation of the kynurenine pathway associated with depression[J]. Chin J Parasitol Parasit Dis, 2023, 41(3): 270-278. (in Chinese) |
(张驰, 陈嘉婷, 辛紫萱, 等. 弓形虫慢性感染小鼠脑转录组分析及与抑郁相关的犬尿氨酸通路的验证[J]. 中国寄生虫学与寄生虫病杂志, 2023, 41(3): 270-278.) | |
[50] |
Sperner-Unterweger B, Kohl C, Fuchs D. Immune changes and neurotransmitters: possible interactions in depression?[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2014, 48: 268-276.
doi: 10.1016/j.pnpbp.2012.10.006 |
[51] |
Tyebji S, Seizova S, Hannan AJ, et al. Toxoplasmosis: a pathway to neuropsychiatric disorders[J]. Neurosci Biobehav Rev, 2019, 96: 72-92.
doi: S0149-7634(18)30370-1 pmid: 30476506 |
[52] |
Falco-Walter J. Epilepsy-definition, classification, pathophysiology, and epidemiology[J]. Semin Neurol, 2020, 40(6): 617-623.
doi: 10.1055/s-0040-1718719 pmid: 33155183 |
[53] |
Feng Y, Wei ZH, Liu C, et al. Genetic variations in GABA metabolism and epilepsy[J]. Seizure, 2022, 101: 22-29.
doi: 10.1016/j.seizure.2022.07.007 pmid: 35850019 |
[54] | Brooks JM, Carrillo GL, Su JM, et al. Toxoplasma gondii infections alter GABAergic synapses and signaling in the central nervous system[J]. mBio, 2015, 6(6): e01428-e01415. |
[55] |
Nelson AR, Sweeney MD, Sagare AP, et al. Neurovascular dysfunction and neurodegeneration in dementia and Alzheimer’s disease[J]. Biochim Biophys Acta, 2016, 1862(5): 887-900.
doi: 10.1016/j.bbadis.2015.12.016 pmid: 26705676 |
[56] |
Bouscaren N, Pilleron S, Mbelesso P, et al. Prevalence of toxoplasmosis and its association with dementia in older adults in Central Africa: a result from the EPIDEMCA programme[J]. Trop Med Int Health, 2018, 23(12): 1304-1313.
doi: 10.1111/tmi.13151 pmid: 30284355 |
[57] | Flegr J, Horáček J. Negative effects of latent toxoplasmosis on mental health[J]. Front Psychiatry, 2020, 10: 1012. |
[58] | El Saftawy EA, Amin NM, Sabry RM, et al. Can Toxoplasma gondii pave the road for dementia?[J]. J Parasitol Res, 2020, 2020: 8859857. |
[1] | 姜文静, 孟雅莉, 赵利娜, 王春苗, 张晓磊. 刚地弓形虫棒状体蛋白18和膜表面抗原30复合核酸疫苗对小鼠的免疫保护作用[J]. 中国寄生虫学与寄生虫病杂志, 2023, 41(5): 532-538. |
[2] | 赵紫琪, 吕芳丽. 蒿甲醚脂质体体外抑制刚地弓形虫增殖作用的研究[J]. 中国寄生虫学与寄生虫病杂志, 2023, 41(4): 446-451. |
[3] | 张驰, 陈嘉婷, 辛紫萱, 杨莉莉, 杨梓瀚, 彭鸿娟. 弓形虫慢性感染小鼠脑转录组分析及与抑郁相关的犬尿氨酸通路的验证[J]. 中国寄生虫学与寄生虫病杂志, 2023, 41(3): 270-278. |
[4] | 杜鹃, 李佳, 吴迪, 余琦, 张玮, 白如念, 郭俊林, 刘庆斌, 雷琪莉, 谷传慧, 王萌, 赵浩军. 2022年北京市犬猫刚地弓形虫感染血清流行病学调查[J]. 中国寄生虫学与寄生虫病杂志, 2023, 41(3): 389-392. |
[5] | 李佳铭, 王艺璇, 杨宁爱, 马慧慧, 兰敏, 刘春兰, 赵志军. 刚地弓形虫ROP16蛋白对MH-S细胞极化和凋亡的影响及其相关机制[J]. 中国寄生虫学与寄生虫病杂志, 2022, 40(5): 579-586. |
[6] | 邹伟浩, 吴蔚玲, 廖远鹏, 陈敏, 彭鸿娟. 刚地弓形虫抗缓殖子期抗原1单克隆抗体的制备与应用[J]. 中国寄生虫学与寄生虫病杂志, 2022, 40(5): 587-593. |
[7] | 代莉莎, 张丽新, 尹昆. 刚地弓形虫诱导宿主精神行为障碍的研究进展[J]. 中国寄生虫学与寄生虫病杂志, 2022, 40(5): 642-646. |
[8] | 王杰, 温红阳, 陈滢, 安然, 罗庆礼, 沈继龙, 都建. 刚地弓形虫巨噬细胞迁移抑制因子基因敲除虫株的构建与鉴定[J]. 中国寄生虫学与寄生虫病杂志, 2022, 40(3): 349-354. |
[9] | 王振勋, 熊思思, 孙夏慧, 王永亮, 潘格, 何深一, 丛华. 刚地弓形虫慢性感染小鼠脑组织中lncRNA102796的差异表达及其作用机制[J]. 中国寄生虫学与寄生虫病杂志, 2022, 40(2): 187-193. |
[10] | 蒋峰, 陈润, 都宁宁, 朱梦怡, 钟昊, 陈辉, 奚旭霞, 湛孝东, 李朝品. 芜湖市区宠物犬、猫刚地弓形虫感染情况调查[J]. 中国寄生虫学与寄生虫病杂志, 2022, 40(1): 124-126. |
[11] | 鲁飞, 卓洵辉, 陆绍红. 顶复门原虫感染与宿主细胞自噬相互作用的研究进展[J]. 中国寄生虫学与寄生虫病杂志, 2021, 39(6): 826-831. |
[12] | 王龙江, 李瑾, 尹昆, 徐超, 刘功振, 黄炳成, 魏庆宽, 孙慧. 刚地弓形虫入侵人包皮成纤维细胞前后转录组差异分析[J]. 中国寄生虫学与寄生虫病杂志, 2021, 39(4): 480-486. |
[13] | 廖文中, 徐李清, 姚礼捷, 陈敏, 彭鸿娟. 弓形虫感染后宿主细胞泛素化蛋白谱变化的特征分析[J]. 中国寄生虫学与寄生虫病杂志, 2021, 39(4): 487-493. |
[14] | 张丽新, 赵桂华, 徐超, 肖婷, 孙慧, 李瑾, 刘功振, 尹昆. 刚地弓形虫RH株速殖子体外入侵小鼠巨噬细胞系感染模型的构建[J]. 中国寄生虫学与寄生虫病杂志, 2021, 39(4): 494-501. |
[15] | 侯永恒, 吕芳丽. 弓形虫感染与宿主细胞自噬的相互作用[J]. 中国寄生虫学与寄生虫病杂志, 2021, 39(4): 537-542. |
阅读次数 | ||||||
全文 |
|
|||||
摘要 |
|
|||||