Original Article

Dysregulation of Ovine Toll-Like Receptors 2 and 4 Expres-sion by Hydatid Cyst-Derived Antigens


Background: Cystic echinococcosis (CE) is a zoonotic disease caused by infection with Echinococcus granulosus. Toll-like receptors (TLRs) as the first line of defense against various parasites play a critical role in sensing and triggering anti-parasite responses.

Methods: The study was conducted at the Department of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Iran in 2019. Ovine peripheral blood mononuclear cells (PBMCs) were stimulated with hydatid cyst-derived antigens including hydatid cyst fluid (HCF), germinal layer antigens (GL), somatic and excretory/secretory (ES) products of protoscoleces (PSC). To investigate whether the expression of TLR2 and TLR4 was altered during exposure to these antigens, PBMCs were stimulated with two different concentrations at different time points.

Results: After exposure of PBMCs to ES and somatic antigens of protoscoleces (PSC) the expression of TLR2 and TLR4 was down-regulated in comparison with control group. Similarly, HCF markedly down-regulated TLR2 and TLR4 transcripts independent of dose and time. GL antigens significantly down-regulated TLR2, while TLR4 expression was up-regulated as compared with control group.

Conclusion: Hydatid cyst-derived antigens could dysregulate the expression of TLR2 and TLR4 in ovine PBMCs, suggesting a possible mechanism to suppress host immunity to establish chronic infection.

1. Brunetti E, Garcia HH, Junghanss T. Cystic Echinococcosis: chronic, complex, and still neglected. PLoS Negl Trop Dis. 2011;5(7):e1146.
2. Siracusano A, Delunardo F, Teggi A, et al . Host-parasite relationship in cystic echinococcosis: an evolving story. Clin Dev Immunol. 2011; 2012:639362.
3. Rigano R, Buttari B, Profumo E, et al. Echinococcus granulosus antigen B impairs human dendritic cell differentiation and polarizes immature dendritic cell maturation towards a Th2 cell response. Infect. Immun. 2007;75(4):1667-78.
4. Wang Y, Wang Q, Lv S, Zhang S. Different protein of Echinococcus granulosus stimulates dendritic induced immune response. Parasitology. 2015;142(07):879-89.
5. Wang Y, Zhou H, Shen Y, 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. BMC Immunol. 2015;16:44.
6. Tuxun T, Ma H-Z, Apaer S, et al. Expression of Toll-Like Receptors 2 and 4 and Related Cytokines in Patients with Hepatic Cystic and Alveolar Echinococcosis. Mediators Inflamm. 2015; 2015:632760.
7. Bellanger AP, Pallandre JR, Gbaguidi-Haore H, et al. Investigating the impact of Echinococcus multilocularis vesicular fluid on human cells from healthy blood donors. J Immunol Methods. 2015;417:52-9.
8. Ashour DS. Toll-like receptor signaling in parasitic infections. Expert Rev Clin Immunol. 2015;11(6):771-80.
9. Siracusano A, Riganò R, Ortona E, et al. Immunomodulatory mechanisms during Echinococcus granulosus infection. Exp Parasitol. 2008; 119(4):483-9.
10. SHAN JY, Tuxun T, LIN RY, et al . TLR2 and TLR4 expression in peripheral blood mononuclear cells of patients with chronic cystic echinococcosis and its relationship with IL‐10. Parasite Immunol. 2011;33(12):692-6.
11. Steers N, Rogan M, Heath S. In‐vitro susceptibility of hydatid cysts of Echinococcus granulosus to nitric oxide and the effect of the laminated layer on nitric oxide production. Parasite Immunol. 2001;23(8):411-7.
12. Robinson RD, Arme C. Echinococcus granulosus: failure of the eosin-exclusion test to demonstrate death of protoscoleces. Ann Trop Med Parasitol. 1985;79(1):117.
13. Smyth J, Davies Z. In vitro culture of the strobilar stage of Echinococcus granulosus (sheep strain): a review of basic problems and results. Int J Parasitol. 1974;4(6):631-644.
14. Pfaffl MW. A new mathematical model for relative quantification in real-time RT–PCR. Nucleic Acids Res. 2001;29(9):e45.
15. Díaz A, Casaravilla C, Barrios AA, et al. Parasite molecules and host responses in cystic echinococcosis. Parasite Immunol. 2016;38(3):193-205.
16. Piconi S, Trabattoni D, Gori A, et al. Immune activation, apoptosis, and Treg activity are associated with persistently reduced CD4+ T-cell counts during antiretroviral therapy. AIDS. 2010;24(13):1991-2000.
17. Zhang W, Ross AG, McManus DP. Mechanisms of immunity in hydatid disease: implications for vaccine development. J Immunol. 2008;181(10):6679-85.
18. Vuitton DA. The ambiguous role of immunity in echinococcosis: protection of the host or of the parasite? Acta Trop. 2003;85(2):119-32.
19. Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. 2010;11(5):373-84.
20. Virginio VG, Monteiro KM, Drumond F, et al. Excretory/secretory products from in vitro-cultured Echinococcus granulosus protoscoleces. Mol Biochem Parasitol. 2012;183(1):15-22.
21. Conchedda M, Gabriele F, Bortoletti G. Immunobiology of cystic echinococcosis. Parassitologia. 2004;46(4):375.
22. Sanchez F, March F, Mercader M, et al. Immunochemical localization of major hydatid fluid antigens in protoscoleces and cysts of Echinococcus granulosus from human origin. Parasite Immunol. 1991;13(6):583-92.
23. Zhang W, Wen H, Li J, et al . Immunology and immunodiagnosis of cystic echino-coccosis: an update. Clin Dev Immunol. 2012;2012:101895.
24. Kanan JH, Chain BM. Modulation of dendritic cell differentiation and cytokine secretion by the hydatid cyst fluid of Echinococcus granulosus. Immunology. 2006;118(2):271-278.
25. Aziz A, Zhang W, Li J, et al. Proteomic characterisation of Echinococcus granulosus hydatid cyst fluid from sheep, cattle and humans. J Proteomics. 2011;74(9):1560-72.
26. Li WG, Wang H, Zhu YM. [Change of splenocyte lymphokines in mice induced by recombinant BCG-Eg95 vaccine against Echinococcus granulosus]. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi. 2007;25(2):109-13.
IssueVol 16 No 2 (2021) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijpa.v16i2.6271
Echinococcus granulosus Hydatid cyst Mononuclear cells Toll-like receptors

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How to Cite
Soleymani N, Taran F, Nazemshirazi MH, Naghibi A, Torabi M, Borji H, Haghparast A. Dysregulation of Ovine Toll-Like Receptors 2 and 4 Expres-sion by Hydatid Cyst-Derived Antigens. Iran J Parasitol. 2021;16(2):219-228.