Research progress on the immune regulation mechanism in alveolar echinococcosis

doi:10.12140/j.issn.1000-7423.2022.01.017

Abstract

Abstract:

Alveolar echinococcosis (AE) is a zoonotic parasitic disease that is endemic worldwide, providing high risk to public health. AE patients are often infected by accidentally eating eggs of Echinococcus multilocularis. AE is highly prevalent in many countries, including China. The most common lesion site is the liver. The invasive growth in the liver causes adjacent liver parenchymal damage, fibrosis and failure. The immune response mediated by macrophages, dendritic cells and T cells are closely related to the occurrence and development of AE. Macrophages and dendritic cells undergo changes in their functions after being stimulated by E. multilocularis, which in turn change CD4 ⁺ T cell subset profiles. These cells are involved in the immune regulation of AE. This article gives an overview of the immune mechanism of AE from the regulation of immune cells and related cytokines perspective, aiming to facilitate therapies against AE.

Key words: Alveolar echinococcosis, Macrophage, CD4⁺ T cell, Dendritic cell

CLC Number:

R532.32

ZHANG Ling-hui, CHEN Gen, CHONG Shi-gui, SHEN Hui, MA Hui, ZHAO Yu-min. Research progress on the immune regulation mechanism in alveolar echinococcosis[J]. CHINESE JOURNAL OF PARASITOLOGY AND PARASITIC DISEASES, 2022, 40(1): 109-113.

Figures/Tables 1

References 44

[1]	World Health Organization. World health statistics 2018: monitoring health for the SDGs, sustainable development goals[M]. Geneva: WHO, 2018: 6-8.
[2]	Deplazes P, Rinaldi L, Alvarez Rojas CA, et al. Global distribution of alveolar and cystic echinococcosis[J]. Adv Parasitol, 2017, 95: 315-493.
[3]	Wang ZH, Wang XM, Liu XQ. Echinococcosis in China, a review of the epidemiology of Echinococcus spp.[J]. Ecohealth, 2008, 5(2): 115-126. doi: 10.1007/s10393-008-0174-0
[4]	Anand S, Hanson K. Disability-adjusted life years: a critical review[J]. J Health Econ, 1997, 16(6): 685-702. pmid: 10176779
[5]	Torgerson PR, Keller K, Magnotta M, et al. The global burden of alveolar echinococcosis[J]. PLoS Negl Trop Dis, 2010, 4(6): e722. doi: 10.1371/journal.pntd.0000722
[6]	Niu FQ, Chong SG, Qin MQ, et al. Mechanism of fibrosis induced by Echinococcus spp.[J]. Diseases, 2019, 7(3): 51. doi: 10.3390/diseases7030051
[7]	Zhao SY, Zhu HH, Wang XQ, et al. Present situation and progress of comprehensive treatments for hepatic alveolar echinococcosis[J]. Chin J Schisto Control, 2019, 31(6): 676-678. (in Chinese)
	(赵顺云, 朱海宏, 王向前, 等. 肝多房棘球蚴病的综合治疗现状和进展[J]. 中国血吸虫病防治杂志, 2019, 31(6): 676-678.)
[8]	Wang J, Gottstein B. Immunoregulation in larval Echinococcus multilocularis infection[J]. Parasite Immunol, 2016, 38(3): 182-192. doi: 10.1111/pim.12292 pmid: 26536823
[9]	Zhang CS, Lin RY, Li ZD, et al. Immune exhaustion of T cells in alveolar echinococcosis patients and its reversal by blocking checkpoint receptor TIGIT in a murine model[J]. Hepatology, 2020, 71(4): 1297-1315. doi: 10.1002/hep.v71.4
[10]	E WJ, Lu YL, Qi BM, et al. Association between serum macrophage polarization-related factors and liver fibrosis in echinococcosis multilocularis[J]. J Clin Hepatol, 2021, 37(12): 2813-2818. (in Chinese)
	(鄂维建, 芦永良, 祁秉民, 等. 血清巨噬细胞极化相关因子与多房棘球蚴病肝纤维化的相关性分析[J]. 临床肝胆病杂志, 2021, 37(12): 2813-2818.)
[11]	Xuan WJ, Qu Q, Zheng B, et al. The chemotaxis of M1 and M2 macrophages is regulated by different chemokines[J]. J Leukoc Biol, 2015, 97(1): 61-69. doi: 10.1189/jlb.1A0314-170R
[12]	Huang L, Ma YF, Wang LJ, et al. Advances in researches on mechanism of macrophage migration inhibitory factor regulating parasite-host immune interaction[J]. Chin J Schisto Control, 2019, 31(4): 446-449. (in Chinese)
	(黄琳, 马元芬, 王灵军, 等. 巨噬细胞迁移抑制因子调节寄生虫与宿主免疫系统相互作用机制的研究进展[J]. 中国血吸虫病防治杂志, 2019, 31(4): 446-449.)
[13]	Wang DX, Wang H, Fan HN, et al. Study on the role of macrophage polarization during E. multilocularis-infection in mice[J]. Chin High Alt Med Biol, 2018, 39(2): 118-122. (in Chinese)
	(王东旭, 王虎, 樊海宁, 等. 巨噬细胞极化在小鼠泡型包虫病中的作用[J]. 中国高原医学与生物学杂志, 2018, 39(2): 118-122.)
[14]	Wang H, Zhang CS, Fang BB, et al. Dual role of hepatic macrophages in the establishment of the Echinococcus multilocularis metacestode in mice[J]. Front Immunol, 2021, 11: 600635. doi: 10.3389/fimmu.2020.600635
[15]	Elchaninov AV, Fatkhudinov TK, Vishnyakova PA, et al. Phenotypical and functional polymorphism of liver resident macrophages[J]. Cells, 2019, 8(9): 1032. doi: 10.3390/cells8091032
[16]	Campana L, Starkey Lewis PJ, Pellicoro A, et al. The STAT3-IL-10-IL-6 pathway is a novel regulator of macrophage efferocytosis and phenotypic conversion in sterile liver injury[J]. J Immunol, 2018, 200(3): 1169-1187. doi: 10.4049/jimmunol.1701247 pmid: 29263216
[17]	Liu YM, Tian FM, Shan JY, et al. Kupffer cells: important participant of hepatic alveolar echinococcosis[J]. Front Cell Infect Microbiol, 2020, 10: 8. doi: 10.3389/fcimb.2020.00008
[18]	Xu K, Wang HJ, Zhang L, et al. Research progress on the mechanisms underlying the impairment of host hepatocytes by Echinococcus multilocularis[J]. Chin J Parasitol Parasit Dis, 2021, 39(2): 256-260. (in Chinese)
	(徐凯, 王海久, 张丽, 等. 多房棘球蚴对宿主肝细胞损害机制的研究进展[J]. 中国寄生虫学与寄生虫病杂志, 2021, 39(2): 256-260.)
[19]	Grubor NM, Jovanova-Nesic KD, Shoenfeld Y. Liver cystic echinococcosis and human host immune and autoimmune follow-up: a review[J]. World J Hepatol, 2017, 9(30): 1176-1189. doi: 10.4254/wjh.v9.i30.1176
[20]	Jenne L, Arrighi JF, Sauter B, et al. Dendritic cells pulsed with unfractionated helminthic proteins to generate antiparasitic cytotoxic T lymphocyte[J]. Parasite Immunol, 2001, 23(4): 195-201. pmid: 11298296
[21]	Xu Y, Pang NN, Guo ZS, et al. The dynamic changes of CD11C⁺CD45RA^- myeloid dendritic cells in the mice infected with Echinococcus multilocularis[J]. J Xinjiang Med Univ, 2016, 39(5): 565-568. (in Chinese)
	(徐岩, 庞楠楠, 郭忠帅, 等. CD11C⁺CD45RA^-髓样树突状细胞在泡球蚴感染小鼠中的水平变化[J]. 新疆医科大学学报, 2016, 39(5): 565-568.)
[22]	Ma XJ, Shang M, Yin QC, et al. Maturation of dendritic cells in peripheral blood of patients with alveolar echinococcosis[J]. Chin Trop Med, 2019, 19(2): 111-115. (in Chinese)
	(马晓静, 尚梅, 尹启超, 等. 泡型肝包虫患者外周血树突状细胞成熟度[J]. 中国热带医学, 2019, 19(2): 111-115.)
[23]	Wei XL, Xu Q, Rexiti FL, et al. Dynamic changes of DC and T cell subsets in mice during Echinococcus multilocularis infection[J]. Cent Eur J Immunol, 2014, 39(1): 19-24.
[24]	Wang Y, Zhou HJ, Shen YJ, et al. Impairment of dendritic cell function and induction of CD4⁺CD25⁺Foxp3⁺ T cells by excretory-secretory products: a potential mechanism of immune evasion adopted by Echinococcus granulosus[J]. BMC Immunol, 2015, 16: 44. doi: 10.1186/s12865-015-0110-3
[25]	Fu Y, Meng R, Jiang T, et al. Effect of multilocular cyst fluid on IDO expression in mouse bone marrow derived dendritic cells[J]. Chin J Zoonoses, 2018, 34(11): 1001-1005. (in Chinese)
	(付永, 孟茹, 姜涛, 等. 小鼠泡型包虫囊液对小鼠骨髓来源树突状细胞表达IDO的影响[J]. 中国人兽共患病学报, 2018, 34(11): 1001-1005.)
[26]	Wang YS, Han XM, Fan W, et al. Study on the immune response of Tibetan patients with echinococcosis in Qinghai[J]. J Pathog Biol, 2017, 12(11): 1070-1073. (in Chinese)
	(王永顺, 韩秀敏, 范雯, 等. 青海省藏族健康人群T淋巴细胞免疫表型及包虫病患者免疫应答研究[J]. 中国病原生物学杂志, 2017, 12(11): 1070-1073.)
[27]	Sungnak W, Wang C, Kuchroo VK. Multilayer regulation of CD4 T cell subset differentiation in the era of single cell genomics[J]. Adv Immunol, 2019, 141: 1-31.
[28]	Koda T, Namba A, Kinoshita M, et al. Sema4A is implicated in the acceleration of Th17 cell-mediated neuroinflammation in the effector phase[J]. J Neuroinflammation, 2020, 17(1): 82. doi: 10.1186/s12974-020-01757-w
[29]	Hou XL, Li LH, Li L, et al. Changes in subsets and functional exhaustion of CD4⁺ T cells in spleens of mice infected with Echinococcus multilocularis[J]. Chin J Parasitol Parasit Dis, 2020, 38(5): 611-618, 624. (in Chinese)
	(侯昕伶, 李玲慧, 李亮, 等. 多房棘球蚴感染小鼠脾CD4⁺ T细胞亚群及其功能耗竭的变化[J]. 中国寄生虫学与寄生虫病杂志, 2020, 38(5): 611-618, 624.)
[30]	Liu HD, Wang HB, Fan HN, et al. Alveolar echinococcosis and immune evasion[J]. Chin J Parasitol Parasit Dis, 2018, 36(6): 655-660. (in Chinese)
	(刘寒冬, 王宏宾, 樊海宁, 等. 多房棘球蚴病的免疫逃避机制[J]. 中国寄生虫学与寄生虫病杂志, 2018, 36(6): 655-660.)
[31]	Wang H, Zhang F, Ma X, et al. Prokaryotic expression and identification of B- and T-cell combined epitopes of Em95 antigen of Echinococcus multilocularis[J]. Int J Clin Exp Pathol, 2014, 7(8): 5117-5122.
[32]	Wang JH, Jebbawi F, Bellanger AP, et al. Immunotherapy of alveolar echinococcosis via PD-1/PD-L1 immune checkpoint blockade in mice[J]. Parasite Immunol, 2018, 40(12): e12596. doi: 10.1111/pim.2018.40.issue-12
[33]	Yu XD, Ye JR. Research progress on the role of Th17/Treg imbalance in hydatid induced allergic reactions[J]. Current Immunol, 2020, 40(1): 81-85. (in Chinese)
	(于晓东, 叶建荣. Th17/Treg失衡在包虫所致过敏反应中作用的研究进展[J]. 现代免疫学, 2020, 40(1): 81-85.)
[34]	Labsi M, Soufli I, Khelifi L, et al. In vivo treatment with IL-17A attenuates hydatid cyst growth and liver fibrogenesis in an experimental model of echinococcosis[J]. Acta Trop, 2018, 181: 6-10. doi: 10.1016/j.actatropica.2018.01.014
[35]	Mejri N, Müller N, Hemphill A, et al. Intraperitoneal Echinococcus multilocularis infection in mice modulates peritoneal CD4⁺ and CD8⁺ regulatory T cell development[J]. Parasitol Int, 2011, 60(1): 45-53. doi: 10.1016/j.parint.2010.10.002
[36]	Zhang LJ, Zhao Y. The regulation of Foxp3 expression in regulatory CD4⁺CD25⁺ T cells: multiple pathways on the road[J]. J Cell Physiol, 2007, 211(3): 590-597. doi: 10.1002/(ISSN)1097-4652
[37]	Wang JH, Cardoso R, Marreros N, et al. Foxp3⁺ T regulatory cells as a potential target for immunotherapy against primary infection with Echinococcus multilocularis eggs[J]. Infect Immun, 2018, 86(10): e00542-18.
[38]	Wang JH, Zhang CS, Wei XF, et al. TGF-β and TGF-β/Smad signaling in the interactions between Echinococcus multilocularis and its hosts[J]. PLoS One, 2013, 8(2): e55379. doi: 10.1371/journal.pone.0055379
[39]	Pang NN, Zhang FB, Ma XM, et al. TGF-β/Smad signaling pathway regulates Th17/Treg balance during Echinococcus multilocularis infection[J]. Int Immunopharmacol, 2014, 20(1): 248-257. doi: 10.1016/j.intimp.2014.02.038
[40]	Zhao H, Pang NN, Ma HM, et al. The levels of cytokines related to Tregs and Th17 cells in Echinococcus multilocularis infection[J]. J Pathog Biol, 2012, 7(2): 129-131, 160. (in Chinese)
	(赵慧, 庞楠楠, 马海梅, 等. 泡球蚴感染小鼠Tregs与Th17细胞相关细胞因子的平衡变化[J]. 中国病原生物学杂志, 2012, 7(2): 129-131, 160.)
[41]	Nono JK, Lutz MB, Brehm K. EmTIP, a T-Cell immunomodulatory protein secreted by the tapeworm Echinococcus multilocularis is important for early metacestode development[J]. PLoS Negl Trop Dis, 2014, 8(1): e2632. doi: 10.1371/journal.pntd.0002632
[42]	Xu MX, Wang XH, Zou Y, et al. Key role of liver sinusoidal endothelial cells in liver fibrosis[J]. Biosci Trends, 2017, 11(2): 163-168. doi: 10.5582/bst.2017.01007
[43]	Gottstein B, Wang JH, Boubaker G, et al. Susceptibility versus resistance in alveolar echinococcosis (larval infection with Echinococcus multilocularis)[J]. Vet Parasitol, 2015, 213(3/4): 103-109. doi: 10.1016/j.vetpar.2015.07.029
[44]	Tuxun T, Apaer S, Ma HZ, et al. Plasma IL-23 and IL-5 as surrogate markers of lesion metabolic activity in patients with hepatic alveolar echinococcosis[J]. Sci Rep, 2018, 8(1): 4417. doi: 10.1038/s41598-018-20301-8