Skip to main content

Advertisement

SpringerLink
Log in

CsRNASET2 is an important component of Clonorchis sinensis responsible for eliciting Th2 immune response

  • Original Paper
  • Published:
Parasitology Research Aims and scope Submit manuscript

Abstract

Many parasites can trigger the host immune response by releasing excretory/secretory proteins (ESPs). CsRNASET2, a glycosylated T2 ribonuclease present in ESPs of Clonorchis sinensis (C. sinensis, Cs), has recently been reported to possess potent effects in regulating mouse dendritic cells (DCs). However, it is unclear whether CsRNASET2 can induce adaptive immune response. In this study, we carried out further investigations on biochemical features of CsRNASET2. Besides, we immunized Balb/c mice with CsRNASET2 and orally infected Balb/c mice with C. sinensis, respectively. Sera of immunized mice were collected and evaluated for specific antibody titers by ELISA. Splenocytes of experimental mice were isolated and stimulated in vitro. The expression levels of IL-4 and IFN-γ in splenocytes of immunized mice and infected mice were detected by ELISA and flow cytometry. Our results showed that the sequence of CsRNASET2 had close relationship with the homologue from Echinococcus multilocularis. The conserved active site (CAS) motifs, active histidine residues, and N-linked glycosylation region of CsRNASET2 were close to each other in the three-dimensional structure. In addition, sera of CsRNASET2 immunized mice had obviously higher levels of specific antibody titers. Splenocytes from both CsRNASET2 immunized mice and C. sinensis infected mice expressed increased levels of IL-4, while the production of IFN-γ exhibited no significant difference. Immunization with CsRNASET2 elicited Th2 immune response by promoting the synthesis of IL-4, consistent with the immune response initiated by infection of C. sinensis. Taken together, these data suggested that CsRNASET2 was important for C. sinensis to trigger Th2 immune response.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Anthony RM, Rutitzky LI, Urban JF, Stadecker MJ, Gause WC (2007) Protective immune mechanisms in helminth infection. Nat Rev Immunol 7:975–987

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B, Palucka K (2000) Immunobiology of dendritic cells. Annu Rev Immunol 18:767–811

    Article  CAS  PubMed  Google Scholar 

  • Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392:245–252

    Article  CAS  PubMed  Google Scholar 

  • Bian M, Li S, Wang X, Xu Y, Chen W, Zhou C, Chen X, He L, Xu J, Liang C, Wu Z, Huang Y, Li X, Yu X (2014) Identification, immunolocalization, and immunological characterization of nitric oxide synthase-interacting protein from Clonorchis sinensis. Parasitol Res 113(5):1749–1757

    Article  PubMed  Google Scholar 

  • Cass CL, Johnson JR, Califf LL, Xu T, Hernandez HJ, Stadecker MJ, Yates JR 3rd, Williams DL (2007) Proteomic analysis of Schistosoma mansoni egg secretions. Mol Biochem Parasitol 155:84–93

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Chen D, Chen J, Huang J, Chen X, Feng D, Liang B, Che Y, Liu X, Zhu C, Li X, Shen H (2010) Epidemiological investigation of Clonorchis sinensis infection in freshwater fishes in the Pearl River Delta. Parasitol Res 107(4):835–839

    Article  PubMed  Google Scholar 

  • Chen J, Xu MJ, Zhou DH, Song HQ, Wang CR, Zhu XQ (2012) Canine and feline parasitic zoonoses in China. Parasit Vectors 5:152

    Article  PubMed Central  PubMed  Google Scholar 

  • Chen W, Wang X, Li X, Lv X, Zhou C, Deng C, Lei H, Men J, Fan Y, Lian C, Yu X (2011) Molecular characterization of cathepsin B from Clonorchis sinensis excretory/secretory products and assessment of its potential for serodiagnosis of clonorchiasis. Parasit Vectors 4:149

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cherwinski HM, Schumacher JH, Brown KD, Mosmann TR (1987) Two types of mouse helper T cell clone. III. Further differences in lymphokine synthesis between Th1 and Th2 clones revealed by RNA hybridization, functionally monospecific bioassays, and monoclonal antibodies. J Exp Med 166(5):1229–1244

    Article  CAS  PubMed  Google Scholar 

  • Chiaramonte MG, Donaldson DD, Cheever AW, Wynn TA (1999) An IL-13 inhibitor blocks the development of hepatic fibrosis during a T-helper type 2-dominated inflammatory response. J Clin Invest 104:777–785

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Deshpande RA, Shankar V (2002) Ribonucleases from T2 family. Crit Rev Microbiol 28:79–122

    Article  CAS  PubMed  Google Scholar 

  • Everts B, Perona-Wright G, Smits HH, Hokke CH, van der Ham AJ, Fitzsimmons CM, Doenhoff MJ, van der Bosch J, Mohrs K, Haas H, Mohrs M, Yazdanbakhsh M, Schramm G (2009) Omega-1, a glycoprotein secreted by Schistosoma mansoni eggs, drives Th2 responses. J Exp Med 206:1673–1680

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Fernandez-Botran R, Sanders VM, Mosmann TR, Vitetta ES (1988) Lymphokine-mediated regulation of the proliferative response of clones of T helper 1 and T helper 2 cells. J Exp Med 168(2):543–558

    Article  CAS  PubMed  Google Scholar 

  • Fertin C, Nicolas JF, Gillery P, Kalis B, Banchereau J, Maquart FX (1991) Interleukin-4 stimulates collagen synthesis by normal and scleroderma fibroblasts in dermal equivalents. Cell Mol Biol 37(8):823–829

    CAS  PubMed  Google Scholar 

  • Hsieh CS, Macatonia SE, Tripp CS, Wolf SF, O’Garra A, Murphy KM (1993) Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. Science 260(5107):547–549

    Article  CAS  PubMed  Google Scholar 

  • Huang L, Lv X, Huang Y, Hu Y, Yan H, Zheng M, Zeng H, Li X, Liang C, Wu Z, Yu X (2014) Identification, sequence analysis, and characterization of serine/threonine protein kinase 17A from Clonorchis sinensis. Parasitol Res 113(5):1713–1723

    Article  PubMed  Google Scholar 

  • Keiser J, Utzinger J (2009) Food-borne trematodiases. Clin Microbiol Rev 22:466–483

    Article  PubMed Central  PubMed  Google Scholar 

  • Le Gros G, Ben-Sasson SZ, Seder R, Finkelman FD, Paul WE (1990) Generation of interleukin-4 (IL-4)-producing cells in vivo and in vitro: IL-2 and IL-4 are required for in vitro generation of IL-4-producing cells. J Exp Med 172(3):921–929

    Article  PubMed  Google Scholar 

  • Lei H, Tian Y, Chen W, Wang X, Li X, Mao Q, Sun J, Li R, Xu Y, Liang C, Huang Y, Yu X (2013) The biochemical and immunological characterization of two serpins from Clonorchis sinensis. Mol Biol Rep 40(6):3977–3985

    Article  CAS  PubMed  Google Scholar 

  • Lipscomb MF, Masten BJ (2002) Dendritic cells: immune regulators in health and disease. Physiol Rev 82:97–130

    CAS  PubMed  Google Scholar 

  • Luhtala N, Parker R (2010) T2 Family ribonucleases: ancient enzymes with diverse roles. Trends Biochem Sci 35:253–259

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lun ZR, Gasser RB, Lai DH, Li AX, Zhu XQ, Yu XB, Fang YY (2005) Clonorchiasis: a key foodborne zoonosis in China. Lancet Infect Dis 5(1):31–41

    Article  PubMed  Google Scholar 

  • Maassen CBM, Boersma WJA, van Holten-Neelen C, Claassen E, Laman JD (2003) Growth phase of orally administered Lactobacillus strains differentially affects IgG1/IgG2a ratio for soluble antigens: implications for vaccine development. Vaccine 21(21–22):2751–2757

    Article  CAS  PubMed  Google Scholar 

  • Maizels RM, Balic A, Gomez-Escobar N, Nair M, Taylor MD, Allen JE (2004) Helminth parasites—masters of regulation. Immunol Rev 201:89–116

    Article  CAS  PubMed  Google Scholar 

  • Maizels RM, Hewitson JP, Smith KA (2012) Susceptibility and immunity to helminth parasites. Curr Opin Immunol 24(4):459–466

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • McKnight AJ, Zimmer GJ, Fogelman I, Wolf SF, Abbas AK (1994) Effects of IL-12 on helper T cell-dependent immune responses in vivo. J Immunol 152(5):2172–2179

    CAS  PubMed  Google Scholar 

  • Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL (1986) Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 136:2348–2357

    CAS  PubMed  Google Scholar 

  • Mosmann TR, Coffman RL (1989) TH1 and TH2 cells different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 7:145–173

    Article  CAS  PubMed  Google Scholar 

  • Mountford AP, Fisher A, Wilson RA (1994) The profile of lgGl and IgG2a antibody responses in mice exposed to Schistosoma mansoni. Parasite Immunol 16:521–527

    Article  CAS  PubMed  Google Scholar 

  • Ouyang W, Rutz S, Crellin NK, Valdez PA, Hymowitz SG (2011) Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annu Rev Immunol 29:71–109

    Article  CAS  PubMed  Google Scholar 

  • Rim HJ (2005) Clonorchiasis: an update. J Helminthol 79(3):269–281

    Article  PubMed  Google Scholar 

  • Seder RA, Paul WE, Davis MM, de St F, Groth B (1992) The presence of interleukin 4 during in vitro priming determines the lymphokine-producing potential of CD4+ T cells from T cell receptor transgenic mice. J Exp Med 176(4):1091–1098

    Article  CAS  PubMed  Google Scholar 

  • Swain SL, Weinberg AD, English M, Huston G (1990) IL-4 directs the synthesis of Th2-like helper effectors. J Immunol 145(11):3796–3806

    CAS  PubMed  Google Scholar 

  • Vercelli D, Jabara HH, Lauener RP, Geha RS (1990) IL-4 inhibits the synthesis of IFN-gamma and induces the synthesis of IgE in human mixed lymphocyte cultures. J Immunol 144(2):570–573

    CAS  PubMed  Google Scholar 

  • Verhoef CM, van Roon JAG, Vianen ME, Bruijnzeel-Koomen CAFM, Lafeber FPJG, Bijlsma JWJ (1998) Mutual antagonism of rheumatoid arthritis and hay fever; a role for type 1/type 2 T cell balance. Ann Rheum Dis 57(5):275–280

  • Wang X, Liang C, Chen W, Fan Y, Hu X, Xu J, Yu X (2009) Experimental model in rats for study on transmission dynamics and evaluation of Clonorchis sinensis infection immunologically, morphologically, and pathologically. Parasitol Res 106:15–21

    Article  PubMed  Google Scholar 

  • Weaver CT, Hawrylowicz CM, Unanue ER (1988) T helper cell subsets require the expression of distinct costimulatory signals by antigen-presenting cells. Proc Natl Acad Sci U S A 85:8181–8185

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wick G, Grundtman C, Mayerl C, Wimpissinger TF, Feichtinger J, Zelger B, Sgonc R, Wolfram D (2013) The immunology of fibrosis. Annu Rev Immunol 31:107–135

    Article  CAS  PubMed  Google Scholar 

  • WHO (1995) Control of foodborne trematode infections. WHO Technical Report Series 849:1–157

    Google Scholar 

  • Xu Y, Chen W, Bian M, Wang X, Sun J, Sun H, Jia F, Liang C, Li X, Zhou X, Huang Y, Yu X (2013) Molecular characterization and immune modulation properties of Clonorchis sinensis-derived RNASET2. Parasit Vectors 6:360

    Article  PubMed Central  PubMed  Google Scholar 

  • Zhu Z, Homer RJ, Wang Z, Chen Q, Geba GP, Wang J, Zhang Y, Elias JA (1999) Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. J Clin Invest 103:779–788

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the Guangdong Natural Science Foundation of China (No. 2014A030313027), the National Important Sci-tech Special Projects (No. 2012ZX10004220), the National Key Basic Research and Development Project of China (973 project; No.2010CB530000), and the National Natural Science Foundation of China (No. 81101270 and No. 81171602).

Conflict of interest

The authors declare that they have no competing interests.

Author information

Author notes

    Authors and Affiliations

    1. Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China

      Yanquan Xu, Jinsi Lin, Meng Bian, Wenjun Chen, Pei Liang, Xiaoyun Wang, Mei Shang, Hongling Qu, Zhongdao Wu, Yan Huang & Xinbing Yu PhD

    2. Key Laboratory for Tropical Diseases Control, Ministry of Education, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China

      Yanquan Xu, Jinsi Lin, Meng Bian, Wenjun Chen, Pei Liang, Xiaoyun Wang, Mei Shang, Hongling Qu, Zhongdao Wu, Yan Huang & Xinbing Yu PhD

    3. Zhongshan Center for Disease Control and Prevention, Zhongshan, 528405, People’s Republic of China

      Jinsi Lin

    Authors
    1. Yanquan Xu
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Jinsi Lin
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Meng Bian
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Wenjun Chen
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Pei Liang
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Xiaoyun Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Mei Shang
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Hongling Qu
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Zhongdao Wu
      View author publications

      You can also search for this author in PubMed Google Scholar

    10. Yan Huang
      View author publications

      You can also search for this author in PubMed Google Scholar

    11. Xinbing Yu PhD
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding authors

    Correspondence to Yan Huang or Xinbing Yu PhD.

    Additional information

    Yanquan Xu and Jinsi Lin contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Xu, Y., Lin, J., Bian, M. et al. CsRNASET2 is an important component of Clonorchis sinensis responsible for eliciting Th2 immune response. Parasitol Res 114, 2371–2379 (2015). https://doi.org/10.1007/s00436-015-4435-x

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s00436-015-4435-x

    Keywords

    Search

    Navigation