Research progress on Toll-like receptors-mediated host immune responses in echinococcosis

doi:10.12140/j.issn.1000-7423.2025.01.019

Abstract

Abstract:

Echinococcosis is a zoonotic parasitic disease caused by the larval stage of Echinococcus species. Echinococcus infection may modulate host immune response and alter host immune microenvironments, thereby triggering immune and inflammatory responses. As a pattern recognition receptor, Toll-like receptors (TLRs) may effectively recognize pathogen-associated molecular patterns and activate downstream signaling pathways by regulating TLR expression and functions, which play an important role in host immune responses to echinococcosis. This review summarizes the latest progress of TLRs in echinococcosis research, with a special emphasis on TLR2 and TLR4, and discusses their potential applications in future treatments of echinococcosis, so as to provide new insights into for echinococcosis prevention and treatment.

Key words: Hepatic echinococcosis, Toll-like receptor, Toll-like receptor 2, Toll-like receptor 4, Immunity

CLC Number:

R532.32

ZHOU Tanfang, ZHU Jiang, XU Xinlu, ZULIPIKAER Tuersunniyazi, KALIBIXIATI Aimulajiang, WEN Hao. Research progress on Toll-like receptors-mediated host immune responses in echinococcosis[J]. CHINESE JOURNAL OF PARASITOLOGY AND PARASITIC DISEASES, 2025, 43(1): 124-128.

Figures/Tables 1

References 44

[1]	Galeh TM, Spotin A, Mahami-Oskouei M, et al. The seroprevalence rate and population genetic structure of human cystic echinococcosis in the Middle East: A systematic review and meta-analysis[J]. Int J Surg, 2018, 51: 39-48. doi: S1743-9191(18)30503-X pmid: 29367032
[2]	Casulli A, Siles-Lucas M, Tamarozzi F. Echinococcus granulosus sensu lato[J]. Trends Parasitol, 2019, 35(8): 663-664.
[3]	Spotin A, Mahami-Oskouei M, Harandi MF, et al. Genetic variability of Echinococcus granulosus complex in various geographical populations of Iran inferred by mitochondrial DNA sequences[J]. Acta Trop, 2017, 165: 10-16. doi: S0001-706X(16)30092-4 pmid: 26948902
[4]	Wen H, Vuitton L, Tuxun T, et al. Echinococcosis: Advances in the 21st century[J]. Clin Microbiol Rev, 2019, 32(2): e00075-18.
[5]	Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity[J]. Cell, 2006, 124(4): 783-801. doi: 10.1016/j.cell.2006.02.015 pmid: 16497588
[6]	Rajasekaran S, Anuradha R, Bethunaickan R. TLR specific immune responses against helminth infections[J]. J Parasitol Res, 2017, 2017: 6865789.
[7]	达哇卓玛, 刘川川, 樊海宁. 细胞程序性死亡在棘球蚴病中的研究进展[J]. 中国寄生虫学与寄生虫病杂志, 2024, 42(2): 259-266, 271. doi: 10.12140/j.issn.1000-7423.2024.02.018
	Dawa ZM, Liu CC, Fan HN. Research on the progress of programmed cell death in echinococcosis[J]. Chin J Parasitol Parasit Dis, 2024, 42(2): 259-266, 271. (in Chinese)
[8]	Li X, Zhang XC, Gong PT, et al. TLR2^-/- mice display decreased severity of giardiasis via enhanced proinflammatory cytokines production dependent on AKT signal pathway[J]. Front Immunol, 2017, 8: 1186.
[9]	Wei R, Li X, Wang XC, et al. Trypanosoma evansi evades host innate immunity by releasing extracellular vesicles to activate TLR2-AKT signaling pathway[J]. Virulence, 2021, 12(1): 2017-2036.
[10]	Kalantari P. The emerging role of pattern recognition receptors in the pathogenesis of malaria[J]. Vaccines (Basel), 2018, 6(1): 13.
[11]	Mukherjee S, Huda S, Sinha Babu SP. Toll-like receptor polymorphism in host immune response to infectious diseases: A review[J]. Scand J Immunol, 2019, 90(1): e12771.
[12]	Gao Y, Nepal N, Jin SZ. Toll-like receptors and hepatitis C virus infection[J]. Hepatobiliary Pancreat Dis Int, 2021, 20(6): 521-529.
[13]	Thompson MR, Kaminski JJ, Kurt-Jones EA, et al. Pattern recognition receptors and the innate immune response to viral infection[J]. Viruses, 2011, 3(6): 920-940. doi: 10.3390/v3060920 pmid: 21994762
[14]	Fitzgerald KA, Kagan JC. Toll-like receptors and the control of immunity[J]. Cell, 2020, 180(6): 1044-1066. doi: S0092-8674(20)30218-X pmid: 32164908
[15]	Pascual M, Calvo-Rodriguez M, Núñez L, et al. Toll-like receptors in neuroinflammation, neurodegeneration, and alcohol-induced brain damage[J]. IUBMB Life, 2021, 73(7): 900-915. doi: 10.1002/iub.2510 pmid: 34033211
[16]	卢想, 谭思由, 张鑫, 等. Toll样受体家族在肝脏缺血再灌注损伤中的研究进展[J]. 河北医药, 2024, 46(18): 2842-2847.
	Lu X, Tan SY, Zhang X, et al. Progress of the Toll-like receptor family in hepatic ischemia-reperfusion injury[J]. Hebei Med J, 2024, 46(18): 2842-2847. (in Chinese)
[17]	Duan TH, Du Y, Xing CS, et al. Toll-like receptor signaling and its role in cell-mediated immunity[J]. Front Immunol, 2022, 13: 812774.
[18]	Lim KH, Staudt LM. Toll-like receptor signaling[J]. Cold Spring Harb Perspect Biol, 2013, 5(1): a011247.
[19]	罗芳, 叶俏. Toll样受体在系统性硬化病皮肤纤维化中的研究进展[J]. 中国现代医生, 2024, 62(24): 118-122.
	Luo F, Ye Q. Research progress of Toll-like receptor in skin fibrosis of systemic sclerosis[J]. China Mod Dr, 2024, 62(24): 118-122. (in Chinese)
[20]	Woolsey ID, Miller AL. Echinococcus granulosus sensu lato and Echinococcus multilocularis: A review[J]. Res Vet Sci, 2021, 135: 517-522. doi: 10.1016/j.rvsc.2020.11.010 pmid: 33246571
[21]	Zhu J, Zhou TF, Meng MG, et al. Ghrelin regulating liver activity and its potential effects on liver fibrosis and echinococcosis[J]. Front Cell Infect Microbiol, 2024, 13: 1324134.
[22]	Bakhtiar NM, Spotin A, Mahami-Oskouei M, et al. Recent advances on innate immune pathways related to host-parasite cross-talk in cystic and alveolar echinococcosis[J]. Parasit Vectors, 2020, 13(1): 232. doi: 10.1186/s13071-020-04103-4 pmid: 32375891
[23]	Yang ZH, Ji SC, Liu L, et al. Promotion of TLR7-MyD88-dependent inflammation and autoimmunity in mice through stem-loop changes in Lnc-Atg16l1[J]. Nat Commun, 2024, 15(1):10224.
[24]	Zhang CS, Wang H, Tuerganaili AJ, et al. Author correction: Targeting myeloid-derived suppressor cells promotes antiparasitic T-cell immunity and enhances the efficacy of PD-1 blockade[J]. Nat Commun, 2024, 15(1): 7374. doi: 10.1038/s41467-024-51832-6 pmid: 39191752
[25]	Jiang M, Broering R, Trippler M, et al. Toll-like receptor-mediated immune responses are attenuated in the presence of high levels of hepatitis B virus surface antigen[J]. J Viral Hepat, 2014, 21(12): 860-872.
[26]	Uraki S, Tameda M, Sugimoto K, et al. Substitution in amino acid 70 of hepatitis C virus core protein changes the adipokine profile via toll-like receptor 2/4 signaling[J]. PLoS One, 2015, 10(6): e0131346.
[27]	Tuxun T, Ma HZ, Apaer S, et al. Expression of toll-like receptors 2 and 4 and related cytokines in patients with hepatic cystic and alveolar echinococcosis[J]. Mediators Inflamm, 2015, 2015: 632760.
[28]	Hou J, Li LL, Dong D, et al. Glycomolecules in Echinococcus granulosus cyst fluid inhibit TLR4-mediated inflammatory responses via c-Raf[J]. Cell Mol Immunol, 2020, 17(4): 423-425.
[29]	Moradkhani MA, Spotin A, Mahami-Oskouei M, et al. A clinical association between Toll-like receptor 2 Arg753Gln polymorphism with recurrent cystic echinococcosis in postsurgery patients: A case control study[J]. Comp Immunol Microbiol Infect Dis, 2019, 66: 101336.
[30]	Mukherjee S, Karmakar S, Babu SP. TLR2 and TLR4 mediated host immune responses in major infectious diseases: A review[J]. Braz J Infect Dis, 2016, 20(2): 193-204. doi: 10.1016/j.bjid.2015.10.011 pmid: 26775799
[31]	Silva-Lagos L, Ijaz A, Buwalda P, et al. Immunostimulatory effects of isomalto/malto-polysaccharides via TLR2 and TLR4 in preventing doxycycline-induced cytokine loss[J]. Carbohydr Polym, 2025, 350: 122980.
[32]	Zhou TF, Xu XL, Zhu J, et al. Association of IL-9 cytokines with hepatic injury in Echinococcus granulosus infection[J]. Biomolecules, 2024, 14(8): 1007.
[33]	Apaer S, Tuxun T, Ma HZ, et al. Expression of Toll-like receptor 2, 4 and related cytokines in intraperitoneally inoculated Balb/C mice with Echinococcus multilocularis[J]. Int J Clin Exp Pathol, 2017, 10(7): 7947-7955.
[34]	阿卜杜萨拉木•艾尼, 吐尔洪江•吐逊, 马海长, 等. Toll样受体mRNA和相关细胞因子在肝多房棘球蚴病患者体内的变化[J]. 中国寄生虫学与寄生虫病杂志, 2016, 34(6): 542-546.
	Abudusalamu AN, Tuerhongjiang TX, MA HZ, et al. Changes of toll-like receptor mRNA and related cytokines in patients with hepatic alveolar echinococcosis[J]. Chin J Parasitol Parasit Dis, 2016, 34(6): 542-546. (in Chinese)
[35]	Noori J, Spotin A, Ahmadpour E, et al. The potential role of Toll-like receptor 4 Asp299Gly polymorphism and its association with recurrent cystic echinococcosis in postoperative patients[J]. Parasitol Res, 2018, 117(6): 1717-1727. doi: 10.1007/s00436-018-5850-6 pmid: 29602972
[36]	Shan JY, Ji WZ, Li HT, et al. TLR2 and TLR4 expression in peripheral blood mononuclear cells of patients with chronic cystic echinococcosis and its relationship with IL-10[J]. Parasite Immunol, 2011, 33(12): 692-696. doi: 10.1111/j.1365-3024.2011.01335.x pmid: 21923667
[37]	Pan W, Xu HW, Hao WT, et al. The excretory-secretory products of Echinococcus granulosus protoscoleces stimulated IL-10 production in B cells via TLR-2 signaling[J]. BMC Immunol, 2018, 19(1): 29.
[38]	Qian YY, Huang FF, Chen SY, et al. Therapeutic effect of recombinant Echinococcus granulosus antigen B subunit 2 protein on sepsis in a mouse model[J]. Parasit Vectors, 2024, 17(1): 467.
[39]	秦敏, 王立英. 阿苯达唑联合药物治疗棘球蚴病的研究进展[J]. 中国寄生虫学与寄生虫病杂志, 2022, 40(5): 647-655. doi: 10.12140/j.issn.1000-7423.2022.05.013
	Qin M, Wang LY. Research progress on combined use of drugs with albendazole in the treatment of echinococcosis[J]. Chin J Parasitol Parasit Dis, 2022, 40(5): 647-655. (in Chinese)
[40]	Yarandi SS, Kulkarni S, Saha M, et al. Intestinal bacteria maintain adult enteric nervous system and nitrergic neurons via Toll-like receptor 2-induced neurogenesis in mice[J]. Gastroenterology, 2020, 159(1): 200-213.e8. doi: S0016-5085(20)30404-2 pmid: 32234538
[41]	Engelmann C, Sheikh M, Sharma S, et al. Toll-like receptor 4 is a therapeutic target for prevention and treatment of liver failure[J]. J Hepatol, 2020, 73(1): 102-112. doi: S0168-8278(20)30028-3 pmid: 31987990
[42]	Nguyen J, Jiao JJ, Smoot K, et al. Toll-like receptor 4: A target for chemoprevention of hepatocellular carcinoma in obesity and steatohepatitis[J]. Oncotarget, 2018, 9(50): 29495-29507. doi: 10.18632/oncotarget.25685 pmid: 30034633
[43]	徐路阳, 张倩, 何冉. 纳米材料与技术在包虫病防治上的应用[J]. 中国兽医学报, 2023, 43(1): 217-222.
	Xu LY, Zhang Q, He R. Application of nanomaterial and nanotechnology in the prevention and treatment of hydatidosis[J]. Chin J Vet Sci, 2023, 43(1): 217-222. (in Chinese)
[44]	李锦田, 罗黎, 林鑫, 等. 细粒棘球蚴感染小鼠血清的代谢组学分析[J]. 中国病原生物学杂志, 2023, 18(7): 770-776.
	Li JT, Luo L, Lin X, et al. Metabolomics analysis of serum in mice infected with Echinococcus granulosus[J]. J Pathog Biol, 2023, 18(7): 770-776. (in Chinese)