寄生虫虫源性成分对宿主的毒理与药理效应

doi:10.12140/j.issn.1000-7423.2022.05.001

中国寄生虫学与寄生虫病杂志 ›› 2022, Vol. 40 ›› Issue (5): 561-571.doi: 10.12140/j.issn.1000-7423.2022.05.001

寄生虫虫源性成分对宿主的毒理与药理效应

徐志鹏¹^,²(), 季旻珺¹^,²^,^*(), 吴观陵¹^,²

1.南京医科大学病原生物学系, 南京 211166
2.江苏省现代病原生物学重点实验室，南京 211166

收稿日期:2022-05-09 修回日期:2022-07-05 出版日期:2022-10-30 发布日期:2022-08-09
通讯作者: 季旻珺
作者简介:徐志鹏（1985-），男，副教授，硕士生导师，从事病原体感染免疫学研究。E-mail：zhipengxu@njmu.edu.cn
基金资助:
国家自然科学基金面上项目(81971965);江苏省自然科学优秀青年基金(BK20211586);江苏省“青蓝工程”(KY101R202127);江苏省卫生健康委科研项目(Z2021004)

The toxicological and pharmacological effects of parasite-derived components on the host

XU Zhi-peng¹^,²(), JI Min-jun¹^,²^,^*(), WU Guan-ling¹^,²

Department of Pathogen Biology, Jiangsu Province Key Laboratory of Modern Pathogen Biology, Nanjing Medical University, Nanjing 211166, China

Received:2022-05-09 Revised:2022-07-05 Online:2022-10-30 Published:2022-08-09
Contact: JI Min-jun
Supported by:
Natural Science Foundation of China(81971965);Natural Science Foundation of Jiangsu Province(BK20211586);Qing Lan Project of Jiangsu Province(KY101R202127);Medical Scientific Research Project of Jiangsu Provincial Health Commission(Z2021004)

摘要/Abstract

摘要：

近年来，一个新的转化医学命题——寄生虫虫源性成分对宿主的毒理与药理效应受到业内的广泛关注。从寄生虫-宿主长期进化过程形成的共适应角度深入理解寄生虫虫源分子对宿主产生的毒理与药理效应，不仅能加深从致病角度理解寄生虫的致病机制，而且有利于从治病角度研发基于虫源性成分的转化应用，已经成为并将继续成为寄生虫学研究领域最热门的研究任务之一。本文回顾近年来几种重要的引起人兽共患病的寄生虫及其虫源性成分诱导及调节宿主免疫代谢相关疾病的毒理与药理效应，并就寄生虫学的研究发展方向提出建议。

关键词: 寄生虫, 虫源性成分, 毒理效应, 药理效应, Treg细胞

Abstract:

In recent years, a new translational medicine proposition, the toxicological and pharmacological effects of parasite-derived components on the host, has received extensive attention. Therefore, an in-depth understanding of parasite-derived molecules’ toxicological and pharmacological effects from the perspective of infection immunology can deepen our understanding of the pathogenesis of parasitic diseases but also facilitate research and development based on the concept of translational medicine. The transformational application value of parasite-derived molecules has become and will continue to be one of the most fantastic research tasks in the field of parasite research. This review focuses on recent advances in the pharmacological effects of zoonotic parasites and their derived components in inducing and regulating host immunometabolism-related diseases, and explores their potential mechanisms.

Key words: Parasite, Parasite-derived molecules, Toxicological effect, Pharmacological effect, Treg cells

中图分类号:

徐志鹏, 季旻珺, 吴观陵. 寄生虫虫源性成分对宿主的毒理与药理效应[J]. 中国寄生虫学与寄生虫病杂志, 2022, 40(5): 561-571.

XU Zhi-peng, JI Min-jun, WU Guan-ling. The toxicological and pharmacological effects of parasite-derived components on the host[J]. Chinese Journal of Parasitology and Parasitic Diseases, 2022, 40(5): 561-571.

图/表 3

表1

寄生虫虫源性分子对宿主的毒理和药理效应

寄生虫种类	虫源分子	毒理或药理效应
原虫
利什曼原虫	金属蛋白酶糖蛋白（63GP63）	作用于巨噬细胞，增加毒力^[9⇓⇓-12]
	外泌体（aExo）	抑制巨噬细胞一氧化氮分泌及活化分子表达^[15]
	r21	诊断犬类和人类利什曼病^[16]
	婴儿利什曼原虫假想蛋白G（rLiHyG）	诊断犬类和人类利什曼病^[17]
	婴儿利什曼原虫假想蛋白J（rLiHyJ）	诊断犬类和人类利什曼病^[18]
	脂磷聚糖3（LPG3）	诱导较高的血清IgG2a抗体水平，有较好的保护力^[19]
	吡哆醛激酶重组蛋白（rPK）	诱导IFN-γ、IL-12、粒细胞巨噬细胞集落刺激因子表达以及特异性IgG2a抗体水平^[20]
弓形虫	致密颗粒蛋白24（GRA24）	诱导p38 MAPK活化和下游IL-12产生^[27]
	致密颗粒蛋白7-V（GRA7-V）	诱导Th1反应，对弓形虫感染具有保护作用^[28]
	棒状体蛋白16（ROP16）	致病与趋化因子CXC基元配体11、TLR3、趋化因子CC基元配体26、人类白细胞抗原E、STAT2等致病候选因子有关^[30]
	重组多表位抗原基因1（rMAG1）	早期诊断弓形虫病^[31]
	重组表面抗原2（rSAG2）	早期诊断弓形虫病^[32]
	重组弓形虫钙依赖性蛋白激酶3（rTgCDPK3）	小鼠模型中具有较好的疫苗保护力^[33]
	六价疫苗分子（pH2，pA4，pE4，pD6，pE6，pH6）	对急性致死性弓形虫病具有较好的保护力^[34]
	弓形虫微线体蛋白16（TgMIC16）	延长RH株感染小鼠的存活时间^[35]
	弓形虫热休克蛋白（TgHSP70）	诱导一氧化氮表达，防止弓形虫脑内包囊形成^[36]
	可溶性速殖子抗原（STAg）	诱导妊娠期母体免疫激活与子代孤独症^[37] 降低H5N1病毒滴度，延长小鼠的生存^[38] 诱导IFN-γ继而减少疟原虫诱导的实验性脑型疟^[39]
	重组致密颗粒蛋白8 （rGRA8）	诱导结肠细胞死亡^[42]
	致密颗粒蛋白15Ⅱ （GRA15Ⅱ）	诱导M1极化，抑制小鼠肝恶性肿瘤的生长^[43]
疟原虫	恶性疟原虫红细胞膜蛋白1（PfEMP1）	引发脑型疟的发生^[47-48]
	间日疟原虫细胞外囊泡（PvEV）	诱导间日疟原虫感染的网织红细胞与人脾成纤维细胞黏附^[49]
	恶性疟原虫沉默SET基因（PfSETvs）	敲除PfSETvs的疟原虫表达PfEMP1蛋白^[50]
	恶性疟原虫裂殖子蛋白复合物（RCR）	恶性疟原虫疫苗的靶点^[52]
	恶性疟原虫热休克蛋白（PfHSP90）	针对PfHSP90研发抗疟药^[56-57]
	结合硫酸软骨素A的可变区2编码蛋白（VAR2CSA）	结合糖胺聚糖直接靶向识别多种肿瘤细胞^[59]
蠕虫
钩虫	巴西钩虫分泌的细胞外囊泡（Nb-EV）	抑制结肠炎病理相关的关键细胞因子^[63]
	美洲钩虫分泌的含netrin结构域的蛋白质1（Na-AIP-1）	抑制2,4,6-三硝基苯磺酸诱导的小鼠结肠炎模型^[64]
	含netrin结构域的蛋白质2（AIP2）	抑制OVA诱导的哮喘小鼠中的气道炎症^[65]
	低相对分子质量代谢物提取物（LMWM-SE）、排泄分泌产物的相对分子质量代谢物（LMWM-ESP）	抑制结肠炎、保护结肠组织结构受损^[66]
	犬钩虫肽1（Acan1）、美洲钩虫肽1（Nak1）	减少2,4,6-三硝基苯磺酸诱导的结肠炎^[67]
血吸虫	SjE16.7	诱导肝脏炎性肉芽肿的形成^[70-71]
	omega-1	诱导肝脏炎性肉芽肿的形成^[72-73]
	可溶性成虫抗原（SWA）	优势诱导巨噬细胞向M1极化^[74]
	可溶性虫卵抗原（SEA）	通过诱导清道夫受体A，促进巨噬细胞M2极化^[75] 通过巨噬细胞诱导Tfh细胞分化^[76] 通过诱导Tfh细胞趋化趋化嗜酸粒细胞^[77]
	Sj16	减缓血吸虫感染诱导的肝脏病理^[78]
	转录反式激活因子丙糖异构酶（Tat-TPI）	减少肝脏中虫卵肉芽肿面积^[79]
	曼氏血吸虫尾蚴蛋白（ASMA）	降低关节炎评分^[83]
	重组日本血吸虫来源的半胱氨酸蛋白酶抑制剂（rSjCystatin）	降低关节炎评分^[84]
	日本血吸虫表位1（SJMHE1）	促进外周髓鞘生长和功能再生^[89] 抑制过敏小鼠的气道炎症^[90] 抑制葡聚糖硫酸钠诱导的小鼠急慢性结肠炎^[91]
绦虫	细粒棘球绦虫重组Kunitz型蛋白酶抑制剂家族1蛋白（EgKI-1）	抑制人类多种癌细胞（包括乳腺癌、黑色素瘤和宫颈癌细胞系）的生长和迁移^[94-95]
	肥头绦虫排泄分泌产物（TcES）	抑制结肠炎相关结肠癌小鼠肿瘤与炎症^[96] 促进一氧化氮的释放，控制寄生虫感染^[97]
	乙酰胆碱酯酶（ACHE）、烟碱型乙酰胆碱受体（nAChR）	新一代驱虫药物的药物靶点^[98]

表1

图1

图2

参考文献 98

[1]	Ebert D,, Fields PD. Host-parasite co-evolution and its genomic signature[J]. Nat Rev Genet, 2020, 21(12): 754-768.
[2]	Wang BF,, Li QY,, Wang JY, et al. Plasmodium infection inhibits tumor angiogenesis through effects on tumor-associated macrophages in a murine implanted hepatoma model[J]. Cell Commun Signal, 2020, 18(1): 157.
[3]	Seo SH,, Kim SG,, Shin JH, et al. Toxoplasma GRA16 inhibits NF-kB activation through PP2A-B55 upregulation in non-small-cell lung carcinoma cells[J]. Int J Mol Sci, 2020, 21(18): 6642.
[4]	Mu Y,, McManus DP,, Hou N, et al. Schistosome infection and schistosome-derived products as modulators for the prevention and alleviation of immunological disorders[J]. Front Immunol, 2021, 12: 619776.
[5]	Maizels RM,, McSorley HJ. Regulation of the host immune system by helminth parasites[J]. J Allergy Clin Immunol, 2016, 138(3): 666-675.
[6]	Chen QJ,, Yin JG. Research and perspectives in parasitology[J]. Chin J Parasitol Parasit Dis, 2007, 25(4): 342-348. (in Chinese)
[6]	( 陈启军,, 尹继刚. 寄生虫学主要研究进展及发展方向[J]. 中国寄生虫学与寄生虫病杂志, 2007, 25(4): 342-348.)
[7]	Poulin R,, Bennett J,, de Angeli Dutra D, et al. Evolutionary signature of ancient parasite pressures, or the ghost of parasitism past[J]. Front Ecol Evol, 2020, 8: 195.
[8]	Mahanta A,, Ganguli P,, Barah P, et al. Integrative approaches to understand the mastery in manipulation of host cytokine networks by protozoan parasites with emphasis on Plasmodium and Leishmania species[J]. Front Immunol, 2018, 9: 296.
[9]	da Silva Vieira T,, Arango Duque G,, Ory K, et al. Leishmania braziliensis: strain-specific modulation of phagosome maturation[J]. Front Cell Infect Microbiol, 2019, 9: 319.
[10]	Yao CQ,, Donelson JE,, Wilson ME. The major surface protease (MSP or GP63) of Leishmania sp. Biosynthesis, regulation of expression, and function[J]. Mol Biochem Parasitol, 2003, 132(1): 1-16.
[11]	Brittingham A,, Morrison CJ,, McMaster WR, et al. Role of the Leishmania surface protease gp63 in complement fixation, cell adhesion, and resistance to complement-mediated lysis[J]. J Immunol, 1995, 155(6): 3102-3111.
[12]	Atayde VD,, Hassani K,, da Silva Lira Filho A, et al. Leishmania exosomes and other virulence factors: impact on innate immune response and macrophage functions[J]. Cell Immunol, 2016, 309: 7-18.
[13]	Silva LP,, Paciello MO,, Aviz Teixeira WP, et al. Immunogenicity of HLA-DR1 and HLA-A2 peptides derived from Leishmania major Gp63 in golden hamsters[J]. Parasite Immunol, 2020, 42(12): e12780.
[14]	Dong G,, Filho AL,, Olivier M. Modulation of host-pathogen communication by extracellular vesicles (EVs) of the protozoan parasite Leishmania[J]. Front Cell Infect Microbiol, 2019, 9: 100.
[15]	Soto-Serna LE,, Diupotex M,, Zamora-Chimal J, et al. Leishmania mexicana: novel insights of immune modulation through amastigote exosomes[J]. J Immunol Res, 2020, 2020: 8894549.
[16]	Karimi Kakh M,, Golchin M,, Kazemi Arababadi M, et al. Application of the Leishmania infantum 21-kDa recombinant protein for the development of an immunochromatographic test[J]. Parasite Immunol, 2020, 42(10): e12770.
[17]	Machado AS,, Ramos FF,, Santos TTO, et al. A new Leishmania hypothetical protein can be used for accurate serodiagnosis of canine and human visceral leishmaniasis and as a potential prognostic marker for human disease[J]. Exp Parasitol, 2020, 216: 107941.
[18]	Oliveira-da-Silva JA,, Machado AS,, Tavares GSV, et al. Biotechnological applications from a Leishmania amastigote-specific hypothetical protein in the canine and human visceral leishmaniasis[J]. Microb Pathog, 2020, 147: 104283.
[19]	Pirdel L,, Farajnia S. A non-pathogenic recombinant Leishmania expressing lipophosphoglycan 3 against experimental infection with Leishmania infantum[J]. Scand J Immunol, 2017, 86(1): 15-22.
[20]	Oliveira-da-Silva JA,, Lage DP,, Ramos FF, et al. Leishmania infantum pyridoxal kinase evaluated in a recombinant protein and DNA vaccine to protects against visceral leishmaniasis[J]. Mol Immunol, 2020, 124: 161-171.
[21]	Salehi M,, Taheri T,, Mohit E, et al. Recombinant Leishmania tarentolae encoding the HPV type 16 E7 gene in tumor mice model[J]. Immunotherapy, 2012, 4(11): 1107-1120.
[22]	Hosseinzadeh S,, Bolhassani A,, Rafati S, et al. A non-pathogenic live vector as an efficient delivery system in vaccine design for the prevention of HPV16 E7-overexpressing cancers[J]. Drug Deliv, 2013, 20(3/4): 190-198.
[23]	Caner A,, Sadğqova A, et al. Targeting of antitumor immune responses with live-attenuated Leishmania strains in breast cancer model[J]. Breast Cancer, 2020, 27(6): 1082-1095.
[24]	Sun H,, Li J,, Wang LJ, et al. Comparative proteomics analysis for elucidating the interaction between host cells and Toxoplasma gondii[J]. Front Cell Infect Microbiol, 2021, 11: 643001.
[25]	Clough B,, Frickel EM. The Toxoplasma parasitophorous vacuole: an evolving host-parasite frontier[J]. Trends Parasitol, 2017, 33(6): 473-488.[PubMed]
[26]	Etheridge RD,, Alaganan A,, Tang KL, et al. The Toxoplasma pseudokinase ROP5 forms complexes with ROP18 and ROP17 kinases that synergize to control acute virulence in mice[J]. Cell Host Microbe, 2014, 15(5): 537-550.
[27]	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.
[28]	Yang CS,, Yuk JM,, Lee YH, et al. Toxoplasma gondii GRA7-induced TRAF6 activation contributes to host protective immunity[J]. Infect Immun, 2015, 84(1): 339-350.
[29]	Sana M,, Rashid M,, Rashid I, et al. Immune response against toxoplasmosis-some recent updates RH: Toxoplasma gondii immune response[J]. Int J Immunopathol Pharmacol, 2022, 36: 3946320221078436.
[30]	Su YJ,, Qiao X,, Wang PT, et al. Gene expression profiling of human lung adenocarcinoma of A549 cells induced by Toxoplasma virulence-related effector ROP16Ⅲ[J]. Chin J Parasitol Parasit Dis, 2021, 39(4): 473-479, 486. (in Chinese)
[30]	( 苏雅静,, 乔霞,, 汪澎涛, 等. 弓形虫毒力相关效应分子ROP16Ⅲ诱导人肺腺癌A549细胞的基因表达谱[J]. 中国寄生虫学与寄生虫病杂志, 2021, 39(4): 473-479, 486.)
[31]	Gatkowska JM,, Dziadek B,, Dziadek J, et al. Recombinant MAG1 protein of Toxoplasma gondii as a diagnostic antigen[J]. Pol J Microbiol, 2015, 64(1): 55-59.
[32]	Sudan V,, Tewari AK,, Singh H. Detection of antibodies against Toxoplasma gondii in Indian cattle by recombinant SAG2 enzyme-linked immunosorbent assay[J]. Acta Parasitol, 2019, 64(1): 148-151.
[33]	Wu MM,, An R,, Chen Y, et al. Vaccination with recombinant Toxoplasma gondii CDPK3 induces protective immunity against experimental toxoplasmosis[J]. Acta Trop, 2019, 199: 105148.
[34]	Sahar EA,, Can H iz SG, et al. Development of a hexavalent recombinant protein vaccine adjuvanted with Montanide ISA 50 V and determination of its protective efficacy against acute toxoplasmosis[J]. BMC Infect Dis, 2020, 20(1): 493.
[35]	Wang LJ,, Xiao T,, Xu C, et al. Protective immune response against Toxoplasma gondii elicited by a novel yeast-based vaccine with microneme protein 16[J]. Vaccine, 2018, 36(27): 3943-3948.
[36]	Czarnewski P,, Araújo ECB,, Oliveira MC, et al. Recombinant tg HSP70 immunization protects against Toxoplasma gondii brain cyst formation by enhancing inducible nitric oxide expression[J]. Front Cell Infect Microbiol, 2017, 7: 142.
[37]	Xu ZP,, Zhang XY,, Chang H, et al. Rescue of maternal immune activation-induced behavioral abnormalities in adult mouse offspring by pathogen-activated maternal Treg cells[J]. Nat Neurosci, 2021, 24(6): 818-830.
[38]	Neal LM,, Knoll LJ. Toxoplasma gondii profilin promotes recruitment of Ly6Chi CCR2⁺ inflammatory monocytes that can confer resistance to bacterial infection[J]. PLoS Pathog, 2014, 10(6): e1004203.
[39]	O’Brien KB,, Schultz-Cherry S,, Knoll LJ. Parasite-mediated upregulation of NK cell-derived gamma interferon protects against severe highly pathogenic H5N1 influenza virus infection[J]. J Virol, 2011, 85(17): 8680-8688.
[40]	Settles EW,, Moser LA,, Harris TH, et al. Toxoplasma gondii upregulates interleukin-12 to prevent Plasmodium berghei-induced experimental cerebral malaria[J]. Infect Immun, 2014, 82(3): 1343-1353.
[41]	Charest H,, Sedegah M,, Yap GS, et al. Recombinant attenuated Toxoplasma gondii expressing the Plasmodium yoelii circumsporozoite protein provides highly effective priming for CD8⁺ T cell-dependent protective immunity against malaria[J]. J Immunol, 2000, 165(4): 2084-2092.
[42]	Kim JS,, Lee D,, Kim D, et al. Toxoplasma gondii GRA8-derived peptide immunotherapy improves tumor targeting of colorectal cancer[J]. Oncotarget, 2020, 11(1): 62-73.
[43]	Li YL,, Poppoe F,, Chen J, et al. Macrophages polarized by expression of ToxoGRA15Ⅱ inhibit growth of hepatic carcinoma[J]. Front Immunol, 2017, 8: 137.
[44]	Su XZ,, Wu J. Zoonotic transmission and host switches of malaria parasites[J]. Zoonoses, 2021, 1(1): 11.
[45]	WHO. World malaria report 2021[J]. Geneva: WHO, 2021: 1-322.
[46]	Feng J,, Zhang L,, Xia ZG, et al. Malaria elimination in China: an eminent milestone in the anti-malaria campaign and challenges in the post-elimination stage[J]. Chin J Parasitol Parasit Dis, 2021, 39(4): 421-428. (in Chinese)
[46]	( 丰俊,, 张丽,, 夏志贵, 等. 中国消除疟疾: 重要里程碑意义及消除后的挑战[J]. 中国寄生虫学与寄生虫病杂志, 2021, 39(4): 421-428.)
[47]	Jensen AR,, Adams Y,, Hviid L. Cerebral Plasmodium falciparum malaria: the role of PfEMP1 in its pathogenesis and immunity, and PfEMP1-based vaccines to prevent it[J]. Immunol Rev, 2020, 293(1): 230-252.
[48]	Turner L,, Lavstsen T,, Berger SS, et al. Severe malaria is associated with parasite binding to endothelial protein C receptor[J]. Nature, 2013, 498(7455): 502-505.
[49]	Toda H,, Diaz-Varela M,, Segui-Barber J, et al. Plasma-derived extracellular vesicles from Plasmodium vivax patients signal spleen fibroblasts via NF-kB facilitating parasite cytoadherence[J]. Nat Commun, 2020, 11(1): 2761.
[50]	Jiang LB,, Mu JB,, Zhang QF, et al. PfSETvs methylation of histone H3K36 represses virulence genes in Plasmodium falciparum[J]. Nature, 2013, 499(7457): 223-227.
[51]	Atcheson E,, Reyes-Sandoval A. Protective efficacy of peptides from Plasmodium vivax circumsporozoite protein[J]. Vaccine, 2020, 38(27): 4346-4354.
[52]	Ragotte RJ,, Higgins MK,, Draper SJ. The RH5-CyRPA-ripr complex as a malaria vaccine target[J]. Trends Parasitol, 2020, 36(6): 545-559.
[53]	Posfai D,, Eubanks AL,, Keim AI, et al. Identification of Hsp90 inhibitors with anti-Plasmodium activity[J]. Antimicrob Agents Chemother, 2018, 62(4): e01799-17.
[54]	Pallavi R,, Roy N,, Nageshan RK, et al. Heat shock protein 90 as a drug target against protozoan infections: biochemical characterization of HSP90 from Plasmodium falciparum and Trypanosoma evansi and evaluation of its inhibitor as a candidate drug[J]. J Biol Chem, 2010, 285(49): 37964-37975.
[55]	Makumire S,, Zininga T,, Vahokoski J, et al. Biophysical analysis of Plasmodium falciparum Hsp70-Hsp90 organising protein (PfHop) reveals a monomer that is characterised by folded segments connected by flexible linkers[J]. PLoS One, 2020, 15(4): e0226657.
[56]	Ramdhave AS,, Patel D,, Ramya I, et al. Targeting heat shock protein 90 for malaria[J]. Mini Rev Med Chem, 2013, 13(13): 1903-1920.
[57]	Tabassum W,, Singh P,, Suthram N, et al. Synergistic action between PfHsp90 inhibitor and PfRad51 inhibitor induces elevated DNA damage sensitivity in the malaria parasite[J]. Antimicrob Agents Chemother, 2021, 65(9): e0045721
[58]	Chen XP,, Qin L,, Hu W, et al. The mechanisms of action of Plasmodium infection against cancer[J]. Cell Commun Signal, 2021, 19(1): 74.
[59]	Salanti A,, Clausen TM,, Agerbæk MØ, et al. Targeting human cancer by a glycosaminoglycan binding malaria protein[J]. Cancer Cell, 2015, 28(4): 500-514.
[60]	Ryan SM,, Eichenberger RM,, Ruscher R, et al. Harnessing helminth-driven immunoregulation in the search for novel therapeutic modalities[J]. PLoS Pathog, 2020, 16(5): e1008508.
[61]	Wu XM,, Dai Y,, Cao J. Progress of research on host immune responses induced by hookworm infection and its potential therapeutic values[J]. Chin J Schisto Control, 2019, 31(5): 560-564. (in Chinese)
[61]	( 吴小珉,, 戴洋,, 曹俊. 钩虫感染诱导宿主免疫反应及其潜在治疗价值研究进展[J]. 中国血吸虫病防治杂志, 2019, 31(5): 560-564.)
[62]	Khudhair Z,, Alhallaf R,, Eichenberger RM, et al. Gastrointestinal helminth infection improves insulin sensitivity, decreases systemic inflammation, and alters the composition of gut microbiota in distinct mouse models of type 2 diabetes[J]. Front Endocrinol (Lausanne), 2021, 11: 606530.
[63]	Eichenberger RM,, Ryan S,, Jones L, et al. Hookworm secreted extracellular vesicles interact with host cells and prevent inducible colitis in mice[J]. Front Immunol, 2018, 9: 850.
[64]	Buitrago G,, Pickering D,, Ruscher R, et al. A netrin domain-containing protein secreted by the human hookworm Necator americanus protects against CD4 T cell transfer colitis[J]. Transl Res, 2021, 232: 88-102.
[65]	Navarro S,, Pickering DA,, Ferreira IB, et al. Hookworm recombinant protein promotes regulatory T cell responses that suppress experimental asthma[J]. Sci Transl Med, 2016, 8(362): 362ra143.
[66]	Wangchuk P,, Shepherd C,, Constantinoiu C, et al. Hookworm-derived metabolites suppress pathology in a mouse model of colitis and inhibit secretion of key inflammatory cytokines in primary human leukocytes[J]. Infect Immun, 2019, 87(4): e00851-18.
[67]	Smallwood TB,, Navarro S,, Cristofori-Armstrong B, et al. Synthetic hookworm-derived peptides are potent modulators of primary human immune cell function that protect against experimental colitis in vivo[J]. J Biol Chem, 2021, 297(1): 100834.
[68]	Liu R,, Wen LY. New progress in basic and clinical research of advanced schistosomiasis[J]. Chin J Parasitol Parasit Dis, 2021, 39(4): 429-436. (in Chinese)
[68]	( 刘蓉,, 闻礼永. 晚期血吸虫病基础和临床研究新进展[J]. 中国寄生虫学与寄生虫病杂志, 2021, 39(4): 429-436.)
[69]	Zhang LJ,, Xu ZM,, Yang F, et al. Endemic status of schistosomiasis in People’s Republic of China in 2020[J]. Chin J Schisto Control, 2021, 33(3): 225-233. (in Chinese)
[69]	( 张利娟,, 徐志敏,, 杨帆, 等. 2020年全国血吸虫病疫情通报[J]. 中国血吸虫病防治杂志, 2021, 33(3): 225-233.)
[70]	Wu CY,, Chen Q,, Fang Y, et al. Schistosoma japonicum egg specific protein SjE16.7 recruits neutrophils and induces inflammatory hepatic granuloma initiation[J]. PLoS Negl Trop Dis, 2014, 8(2): e2703.
[71]	Fang Y,, Wu CY,, Chen Q, et al. SjE16.7 activates macrophages and promotes Schistosoma japonicum egg-induced granuloma development[J]. Acta Trop, 2015, 149: 49-58.
[72]	Takaki KK,, Roca FJ,, Schramm G, et al. Tumor necrosis factor and Schistosoma mansoni egg antigen Omega-1 shape distinct aspects of the early egg-induced granulomatous response[J]. PLoS Negl Trop Dis, 2021, 15(1): e0008814.
[73]	Hagen J,, Young ND,, Every AL, et al. Omega-1 knockdown in Schistosoma mansoni eggs by lentivirus transduction reduces granuloma size in vivo[J]. Nat Commun, 2014, 5: 5375.
[74]	Zhu JF,, Xu ZP,, Chen XJ, et al. Parasitic antigens alter macrophage polarization during Schistosoma japonicum infection in mice[J]. Parasit Vectors, 2014, 7: 122.
[75]	Xu ZP,, Xu L,, Li W, et al. Innate scavenger receptor-A regulates adaptive T helper cell responses to pathogen infection[J]. Nat Commun, 2017, 8: 16035.
[76]	Chen XJ,, Yang XW,, Li Y, et al. Follicular helper T cells promote liver pathology in mice during Schistosoma japonicum infection[J]. PLoS Pathog, 2014, 10(5): e1004097.
[77]	Chen XJ,, Xu ZP,, Wei C, et al. Follicular helper T cells recruit eosinophils into host liver by producing CXCL12 during Schistosoma japonicum infection[J]. J Cell Mol Med, 2020, 24(4): 2566-2572.
[78]	Shen J,, Wang LF,, Peng M, et al. Recombinant Sj16 protein with novel activity alleviates hepatic granulomatous inflammation and fibrosis induced by Schistosoma japonicum associated with M2 macrophages in a mouse model[J]. Parasit Vectors, 2019, 12(1): 457.
[79]	Zhang WY,, Luo XF,, Zhang F, et al. SjTat-TPI facilitates adaptive T-cell responses and reduces hepatic pathology during Schistosoma japonicum infection in BALB/c mice[J]. Parasit Vectors, 2015, 8: 664.
[80]	Osada Y,, Shimizu S,, Kumagai T, et al. Schistosoma mansoni infection reduces severity of collagen-induced arthritis via down-regulation of pro-inflammatory mediators[J]. Int J Parasitol, 2009, 39(4): 457-464.
[81]	He YK,, Li J,, Zhuang WJ, et al. The inhibitory effect against collagen-induced arthritis by Schistosoma japonicum infection is infection stage-dependent[J]. BMC Immunol, 2010, 11: 28.
[82]	Osada Y,, Horie Y,, Nakae S, et al. STAT6 and IL-10 are required for the anti-arthritic effects of Schistosoma mansoni via different mechanisms[J]. Clin Exp Immunol, 2019, 195(1): 109-120.
[83]	Eissa MM,, Mostafa DK,, Ghazy AA, et al. Anti-arthritic activity of Schistosoma mansoni and Trichinella spiralis derived-antigens in adjuvant arthritis in rats: role of FOXP3⁺ Treg cells[J]. PLoS One, 2016, 11(11): e0165916.
[84]	Liu F,, Cheng WS,, Pappoe F, et al. Schistosoma japonicum cystatin attenuates murine collagen-induced arthritis[J]. Parasitol Res, 2016, 115(10): 3795-3806.
[85]	Sun XL,, Zhang LB,, Wang JX, et al. Schistosoma japonicum protein SjP40 inhibits TGF-β1-induced activation of hepatic stellate cells[J]. Parasitol Res, 2015, 114(11): 4251-4257.
[86]	Zhou XH,, Wu JY,, Huang XQ, et al. Identification and characterization of Schistosoma japonicum Sjp40, a potential antigen candidate for the early diagnosis of schistosomiasis[J]. Diagn Microbiol Infect Dis, 2010, 67(4): 337-345.
[87]	Ren JL,, Hu LZ,, Yang J, et al. Novel T-cell epitopes on Schistosoma japonicum SjP40 protein and their preventive effect on allergic asthma in mice[J]. Eur J Immunol, 2016, 46(5): 1203-1213.
[88]	Ni YY,, Xu ZP,, Li C, et al. Therapeutic inhibition of miR-802 protects against obesity through AMPK-mediated regulation of hepatic lipid metabolism[J]. Theranostics, 2021, 11(3): 1079-1099.
[89]	Ma YB,, Wei C,, Qi X, et al. Schistosoma japonicum-derived peptide SJMHE1 promotes peripheral nerve repair through a macrophage-dependent mechanism[J]. Am J Transl Res, 2021, 13(3): 1290-1306.
[90]	Zhang WZ,, Li L,, Zheng Y, et al. Schistosoma japonicum peptide SJMHE1 suppresses airway inflammation of allergic asthma in mice[J]. J Cell Mol Med, 2019, 23(11): 7819-7829.
[91]	Shan WQ,, Zhang WZ,, Xue F, et al. Schistosoma japonicum peptide SJMHE1 inhibits acute and chronic colitis induced by dextran sulfate sodium in mice[J]. Parasit Vectors, 2021, 14(1): 455.
[92]	Zhang S,, Gong TT,, Liu FH, et al. Global, regional, and national burden of endometrial cancer, 1990—2017: results from the global burden of disease study, 2017[J]. Front Oncol, 2019, 9: 1440.
[93]	Arora N,, Prasad A. Taenia solium proteins: a beautiful kaleidoscope of pro and anti-inflammatory antigens[J]. Expert Rev Proteomics, 2020, 17(7/8): 609-622.
[94]	Ranasinghe SL,, Boyle GM,, Fischer K, et al. Kunitz type protease inhibitor EgKI-1 from the canine tapeworm Echinococcus granulosus as a promising therapeutic against breast cancer[J]. PLoS One, 2018, 13(8): e0200433.
[95]	Ranasinghe SL,, Rivera V,, Boyle GM, et al. Kunitz type protease inhibitor from the canine tapeworm as a potential therapeutic for melanoma[J]. Sci Rep, 2019, 9(1): 16207.
[96]	Callejas BE,, Mendoza-Rodríguez MG,, Villamar-Cruz O, et al. Helminth-derived molecules inhibit colitis-associated colon cancer development through NF-κB and STAT3 regulation[J]. Int J Cancer, 2019, 145(11): 3126-3139.
[97]	Fan XM,, Zhou BY. Research advances on the relationship between cestode excretory/secretory products and host immune response[J]. Chin J Parasitol Parasit Dis, 2020, 38(1): 128-133. (in Chinese)
[97]	( 范贤敏,, 周必英. 绦虫排泄分泌物与宿主免疫效应的相关研究进展[J]. 中国寄生虫学与寄生虫病杂志, 2020, 38(1): 128-133.)
[98]	Liu CC,, Fan HN,, Ma L, et al. Advances in acetylcholinesterase and nicotinic acetylcholine receptors as potential drug targets in Echinococcus and other parasitic tapeworms[J]. Chin J Zoonoses, 2019, 35(12): 1122-1129. (in Chinese)
[98]	( 刘川川,, 樊海宁,, 马兰, 等. 棘球绦虫和其它寄生性绦虫乙酰胆碱酯酶和烟碱型乙酰胆碱受体作为潜在药物靶点的研究进展[J]. 中国人兽共患病学报, 2019, 35(12): 1122-1129.)

寄生虫虫源性成分对宿主的毒理与药理效应

The toxicological and pharmacological effects of parasite-derived components on the host

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 3

参考文献 98

相关文章 15

编辑推荐

Metrics

本文评价

[1]	滕雪娇, 黄浩, 朱剑辉, 钟晨, 陈晨, 吴家兵, 邓舒. 2013—2023年安徽省传染病网络直报系统法定寄生虫病报告情况分析[J]. 中国寄生虫学与寄生虫病杂志, 2025, 43(1): 91-96.
[2]	陈萌, 陶洪, 李彦忠, 张娟, 周晓梅. 云南省布朗族聚居地区人群肠道寄生虫感染情况调查[J]. 中国寄生虫学与寄生虫病杂志, 2024, 42(5): 623-628.
[3]	徐凯, 陈力, 林登峰. 寄生虫及其相关物治疗炎症性肠病转归进展[J]. 中国寄生虫学与寄生虫病杂志, 2024, 42(3): 407-412.
[4]	李昆雷, 夏俊, 邱美龄, 胡美荷, 吉古孝安, 候梦丹, 翟少华. 抗寄生虫中药活性成分体外抗细粒棘球蚴作用[J]. 中国寄生虫学与寄生虫病杂志, 2024, 42(2): 191-198.
[5]	王强, 许静, 夏志贵, 韩帅, 张仪, 钱门宝, 李石柱, 周晓农. 我国重点寄生虫病疫情形势及防控工作重点[J]. 中国寄生虫学与寄生虫病杂志, 2024, 42(1): 1-7.
[6]	郝瑜婉, 田添, 朱泽林, 陈怡君, 朱慧慧, 王强, 李石柱, 周晓农. 全国疾控机构重点寄生虫病防治能力建设现状分析[J]. 中国寄生虫学与寄生虫病杂志, 2024, 42(1): 83-90.
[7]	国家感染性疾病临床医学研究中心, 国家传染病医学中心撰写组. 食源性寄生虫病诊治专家共识（2023）[J]. 中国寄生虫学与寄生虫病杂志, 2023, 41(6): 653-668.
[8]	马悦, 赵保才, 周佳丽, 胡峻豪, 赵洪喜. miRNA在顶复门寄生虫感染中调控作用的研究进展[J]. 中国寄生虫学与寄生虫病杂志, 2023, 41(6): 749-755.
[9]	杨金颋, 黄晓宾, 王玉娟, 郭宪国, 张现政, 杨慧娟, 郑小燕. 云南大理毛腿鼠耳蝠体表寄生虫感染情况及其体表寄生蛛蝇的形态特征和系统进化分析[J]. 中国寄生虫学与寄生虫病杂志, 2023, 41(4): 452-458.
[10]	李小丽, 栗绍刚, 吴赵永. 双叶槽绦虫肠道感染患者的临床表现特征分析[J]. 中国寄生虫学与寄生虫病杂志, 2023, 41(4): 459-463.
[11]	王峰, 吴凡, 李琳琳, 黄青青. 安徽省芜湖市野鼠寄生虫感染情况分析[J]. 中国寄生虫学与寄生虫病杂志, 2023, 41(4): 516-519.
[12]	谢宜, 王莹, 王旭, 施丹丹, 付梅花, 李春阳, 伍卫平, 丹巴泽里, 廖沙, 张凯歌, 邓雪莹, 官亚宜. 基于高通量测序的家犬粪便寄生虫病原调查[J]. 中国寄生虫学与寄生虫病杂志, 2023, 41(3): 325-330.
[13]	盛慧锋, 周晓农, 余森海, 汤林华, 冯正, 李石柱, 薛纯良, 吴观陵, 余新炳, 温廷桓, 程训佳, 潘卫庆, 胡薇, 苏川, 汪天平, 吴忠道, 陈勤, 张争艳, 戴菁, 李菂, 刘雨舟, 曹建平. 《中国寄生虫学与寄生虫病杂志》创刊40年发展历程[J]. 中国寄生虫学与寄生虫病杂志, 2023, 41(1): 1-9.
[14]	陈琳, 朱继峰, 邱竞帆, 徐志鹏, 张东辉, 陈璐, 何健, 李伟, 杨坤, 季旻珺. 寓全健康理念于血吸虫病防控虚拟仿真项目建设[J]. 中国寄生虫学与寄生虫病杂志, 2023, 41(1): 81-84.
[15]	吴晓莹, 胡媛, 曹建平. 寄生虫病表位疫苗研究进展[J]. 中国寄生虫学与寄生虫病杂志, 2023, 41(1): 98-102.