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

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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

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