Skip to main content

Advertisement

SpringerLink
Log in

Protective effect and mechanism of Schistosoma japonicum soluble egg antigen against type 1 diabetes in NOD mice

  • Original Article
  • Published:
International Journal of Diabetes in Developing Countries Aims and scope Submit manuscript

Abstract

Objective

To study the effect and mechanism of Schistosoma japonicum soluble egg antigen (SEA) on protecting against type 1 diabetes, 4-week-old female BALB/c and NOD mice were divided randomly into four groups: BALB/c control, BALB/c treated with SEA, NOD control, and NOD treated with SEA.

Methods

Treated mice were injected intraperitoneally with 50 μg of SEA twice a week for 6 weeks, and control mice received the same volume of phosphate-buffered saline. Blood glucose in all mice was determined weekly from 8 weeks of age. Flow cytometry was used to detect the percentages of regulatory T cells of splenocytes in each group. Enzyme-linked immunosorbent assays were used to detect the levels of interferon-γ, interleukin (IL)-2, IL-4, and IL-5 in splenic cell culture supernatants.

Results

Compared with those of the NOD group, the blood glucose level and percentage incidence of diabetes in NOD mice treated with SEA decreased significantly. This indicated that SEA treatment prevented spontaneous type 1 diabetes. After SEA administration, the frequency of splenic regulatory T cells increased significantly, and the secretion of IL-4 and IL-5 by splenic cells increased.

Conclusions

These results demonstrated that SEA can prevent type 1 diabetes by enhancing regulatory T cells and the T helper 2 cell immune response in NOD mice.

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

Similar content being viewed by others

References

  1. Saeedi P, Petersohn I, Salpea P, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the International Diabetes Federation Diabetes Atlas, 9(th) edition. Diabetes Res Clin Pract. 2019;157:107843.

    PubMed  Google Scholar 

  2. Vukovic R, Jesic MD, Vorgucin I, et al. First report on the nationwide incidence of type 1 diabetes and ketoacidosis at onset in children in Serbia: a multicenter study. Eur J Pediatr. 2018;177:1155–62.

    Article  CAS  Google Scholar 

  3. Weinstock JV, Elliott DE. Helminth infections decrease host susceptibility to immune-mediated diseases. J Immunol. 2014;193:3239–47.

    Article  CAS  Google Scholar 

  4. Amdare NP, Khatri VK, Yadav RSP, et al. Therapeutic potential of the immunomodulatory proteins Wuchereria bancrofti L2 and Brugia malayi abundant larval transcript 2 against streptozotocin-induced type 1 diabetes in mice. J Helminthol. 2017;91:539–48.

    Article  CAS  Google Scholar 

  5. Osada Y, Yamada S, Nabeshima A, et al. Heligmosomoides polygyrus infection reduces severity of type 1 diabetes induced by multiple low-dose streptozotocin in mice via STAT6- and IL-10-independent mechanisms. Exp Parasitol. 2013;135:388–96.

    Article  CAS  Google Scholar 

  6. Lund ME, O’Brien BA, Hutchinson AT, et al. Secreted proteins from the helminth Fasciola hepatica inhibit the initiation of autoreactive T cell responses and prevent diabetes in the NOD mouse. PLoS One. 2014;9:e86289.

  7. El-Wakil HS, Aboushousha TS, El Haddad O, et al. Effect of Schistosoma mansoni egg deposition on multiple low doses streptozotocin induced insulin dependent diabetes. J Egypt Soc Parasitol. 2002;32:987–1002.

    PubMed  Google Scholar 

  8. Osada Y, Fujiyama T, Kamimura N, et al. Dual genetic absence of STAT6 and IL-10 does not abrogate anti-hyperglycemic effects of Schistosoma mansoni in streptozotocin-treated diabetic mice. Exp Parasitol. 2017;177:1–12.

    Article  CAS  Google Scholar 

  9. Tang CL, Yu XH, Li Y, et al. Schistosoma japonicum soluble egg antigen protects against type 2 diabetes in Lepr (db/db) mice by enhancing regulatory T cells and Th2 cytokines. Front Immunol. 2019;10:1471.

    Article  CAS  Google Scholar 

  10. Huan W, Ya-Jing L, Yan-Ru G, et al. Changes of liver fibrosis-related miRNAs induced by soluble egg antigen of Schistosoma japonicum. Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi. 2017;29:192–6.

    PubMed  Google Scholar 

  11. Zaccone P, Fehérvári Z, Jones FM, et al. Schistosoma mansoni antigens modulate the activity of the innate immune response and prevent onset of type 1 diabetes. Eur J Immunol. 2003;33:1439–49.

    Article  CAS  Google Scholar 

  12. Delovitch TL, Singh B. The nonobese diabetic mouse as a model of autoimmune diabetes: immune dysregulation gets the NOD. Immunity. 1997;7:727–38.

    Article  CAS  Google Scholar 

  13. Cooke A, Tonks P, Jones FM, et al. Infection with Schistosoma mansoni prevents insulin dependent diabetes mellitus in non-obese diabetic mice. Parasite Immunol. 1999;21:169–76.

    Article  CAS  Google Scholar 

  14. Maizels RM. Parasitic helminth infections and the control of human allergic and autoimmune disorders. Clin Microbiol Infect. 2016;22:481–6.

    Article  CAS  Google Scholar 

  15. Zaccone P, Burton OT, Gibbs SE, et al. The S. mansoni glycoprotein ω-1 induces Foxp3 expression in NOD mouse CD4+T cells. Eur J Immunol. 2011;41:2709–18.

    Article  CAS  Google Scholar 

  16. Sgouroudis E, Piccirillo CA. Control of type 1 diabetes by CD4+Foxp3+ regulatory T cells: lessons from mouse models and implications for human disease. Diabetes Metab Res Rev. 2009;25:208–18.

    Article  CAS  Google Scholar 

  17. Kukreja A, Cost G, Marker J, et al. Multiple immuno-regulatory defects in type-1 diabetes. J Clin Invest. 2002;109:131–40.

    Article  CAS  Google Scholar 

  18. Brode S, Raine T, Zaccone P, et al. Cyclophosphamide-induced type-1 diabetes in the NOD mouse is associated with a reduction of CD4+CD25+Foxp3+ regulatory T cells. J Immunol. 2006;177:6603–12.

    Article  CAS  Google Scholar 

  19. El-Ahwany E, Bauiomy IR, Nagy F, et al. T regulatory cell responses to immunization with a soluble egg antigen in Schistosoma mansoni-infected mice. Korean J Parasitol. 2012;50:29–35.

    Article  CAS  Google Scholar 

  20. Zhou S, Jin X, Chen X, et al. Heat shock protein 60 in eggs specifically induces Tregs and reduces liver immunopathology in mice with Schistosomiasis japonica. PLoS One. 2015;10:e0139133.

    Article  Google Scholar 

  21. Pacífico LG, Marinho FA, Fonseca CT, et al. Schistosoma mansoni antigens modulate experimental allergic asthma in a murine model: a major role for CD4+ CD25+ Foxp3+ T cells independent of interleukin-10. Infect Immun. 2009;77:98–107.

    Article  Google Scholar 

  22. Hasby EA, Hasby Saad MA, Shohieb Z, et al. FoxP3+ T regulatory cells and immunomodulation after Schistosoma mansoni egg antigen immunization in experimental model of inflammatory bowel disease. Cell Immunol. 2015;295:67–76.

    Article  CAS  Google Scholar 

  23. Kikodze N, Pantsulaia I, Rekhviashvili Kh, et al. Cytokines and T regulatory cells in the pathogenesis of type 1 diabetes. Georgian Med News. 2013;222:29–35.

    Google Scholar 

  24. Mueller R, Krahl T, Sarvetnick N. Pancreatic expression of interleukin-4 abrogates insulitis and autoimmune diabetes in nonobese diabetic (NOD) mice. J Exp Med. 1996;184:1093–9.

    Article  CAS  Google Scholar 

  25. Okano M, Satoskar AR, Nishizaki K, et al. Induction of Th2 responses and IgE is largely due to carbohydrates functioning as adjuvants on Schistosoma mansoni egg antigens. J Immunol. 1999;163:6712–7.

    CAS  PubMed  Google Scholar 

  26. Everts B, Perona-Wright G, Smits HH, et al. Omega-1, a glycoprotein secreted by Schistosoma mansoni eggs, drives Th2 responses. J Exp Med. 2009;206:1673–80.

    Article  CAS  Google Scholar 

  27. Maron R, Palanivel V, Weiner HL, et al. Oral administration of schistosome egg antigens and insulin B-chain generates and enhances Th2-type responses in NOD mice. Clin Immunol Immunopathol. 1998;87:85–92.

    Article  CAS  Google Scholar 

  28. Zaccone P, Burton OT, Gibbs S, et al. Immune modulation by Schistosoma mansoni antigens in NOD mice: effects on both innate and adaptive immune systems. J Biomed Biotechnol. 2010;2010:1–13.

  29. Jackson-Thompson BM, Torrero M, Mitre BK, et al. Axenic Caenorhabditis elegans antigen protects against development of type-1 diabetes in NOD mice. J Transl Autoimmun. 2020;3:100065.

    Article  Google Scholar 

  30. Yan K, Wang B, Zhou H, et al. Amelioration of type 1 diabetes by recombinant fructose-1,6-bisphosphate aldolase and cystatin derived from Schistosoma japonicum in a murine model. Parasitol Res. 2020;119:203–14.

    Article  Google Scholar 

Download references

Funding

This research was supported by a National Natural Science Foundation of China grant (No. 82070810), Science and Technology Research Project of Hubei Provincial Department of Education (No. B2019362), Research Projects of Hubei Provincial Health Commission (No. WJ2017X30), and Independent Research Talents Fund Project of City College, Wuhan University of Science and Technology (No. 2019CYBSKY002). This research was funded by the scientific research subject of the health and family planning commission of Wuhan Municipality (WX20D01 and EX20D21).

Author information

Author notes

  1. Li-xia Wang and Qun Pan contributed equally to this work.

Authors and Affiliations

  1. Wuhan Pulmonary Hospital, Wuhan Institute for Tuberculosis Control, Wuhan, 430030, China

    Li-xia Wang & Chun-lan Zheng

  2. Medical Department, City College, Wuhan University of Science and Technology, Wuhan, 430083, China

    Yan-ru Gao

  3. Wuchang Hospital affiliated to Wuhan University of Science and Technology, Wuhan, 430063, China

    Qun Pan, Chun-lian Tang & Rong-hui Zhang

  4. Department of Endocrinology, Wuchang Hospital Affiliated To Wuhan University of Science and Technology, Wuhan, 430063, China

    Yan-hong Li

Authors
  1. Li-xia Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yan-ru Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qun Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chun-lian Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rong-hui Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yan-hong Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chun-lan Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yan-hong Li or Chun-lan Zheng.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, Lx., Gao, Yr., Pan, Q. et al. Protective effect and mechanism of Schistosoma japonicum soluble egg antigen against type 1 diabetes in NOD mice. Int J Diabetes Dev Ctries 42, 363–368 (2022). https://doi.org/10.1007/s13410-021-00970-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13410-021-00970-4

Keywords

Search

Navigation