Skip to main content
SpringerLink
Log in

The Protective Effect of the Recombinant 53-kDa Protein of Trichinella spiralis on Experimental Colitis in Mice

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

Helminth infection has been proven to reduce the severity of experimental inflammatory bowel disease (IBD). The excretory-secretory proteins of helminths play an important role in the process of immunomodulation.

Aims

In the present study, we aimed to investigate the protective potential of recombinant Trichinella spiralis (TS) 53-kDa protein (rTsP53), a component of excretory-secretory proteins, on experimental colitis in mice.

Methods

BALB/c mice were treated subcutaneously with 50 μg rTsP53 three times at an interval of 5 days. Colitis was induced by intrarectal administration of 5 mg trinitrobenzene sulfonic acid (TNBS). Disease activities and macroscopic and microscopic scores were evaluated. To determine immune response provoked by rTsP53, we measured specific IgG1 and IgG2a values against rTsP53 in sera of mice. We also detected cytokine profiles as well as the markers of alternatively activated macrophages (M2) in mice.

Results

RTsP53 ameliorated significantly the disease activity index (DAI) as well as the macroscopic and microscopic scores. IgG1 but not IgG2a was the predominant specific antibody detected in the sera of immunized mice, indicating the potential of stimulating T-helper (Th) 2 bias response by rTsP3. Pre-treatment with rTsP53 decreased serum Th1 cytokines (TNF-a, IFN-γ) and elevated serum levels of serum Th2 cytokines (IL-4, IL-13); it also decreased colonic Th1 cytokines (TNF-α, IL-6) and colonic regulatory cytokines (IL-10, TGF-β1). RTsP53 increased colonic M2 markers, arginase-1 (Arg-1), and found in inflammatory zone 1 (FIZZ1), compared to mice without rTsP53 pretreatment.

Conclusions

RTsP53 is a potential protective agent for IBD.

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.

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

Similar content being viewed by others

References

  1. Podolsky DK. Inflammatory bowel disease. N Engl J Med. 2002;347:417–429.

    Article  PubMed  CAS  Google Scholar 

  2. Wurzelmann JI, Lyles CM, Sandler RS. Childhood infections and the risk of inflammatory bowel disease. Dig Dis Sci. 1994;39:555–560.

    Article  PubMed  CAS  Google Scholar 

  3. Elliott DE, Urban JF Jr, Argo CK, Weinstock JV. Does the failure to acquire helminthic parasites predispose to Crohn’s disease? FASEB J. 2000;14:1848–1855.

    Article  PubMed  CAS  Google Scholar 

  4. Fox JG, Beck P, Dangler CA, et al. Concurrent enteric helminth infection modulates inflammation and gastric immune responses and reduces Helicobacter-induced gastric atrophy. Nat Med. 2000;6:536–542.

    Article  PubMed  CAS  Google Scholar 

  5. Khan WI, Blennerhasset PA, Varghese AK, et al. Intestinal nematode infection ameliorates experimental colitis in mice. Infect Immun. 2002;70:5931–5937.

    Article  PubMed  CAS  Google Scholar 

  6. Elliott DE, Li J, Blum A, et al. Exposure to schistosome eggs protects mice from TNBS-induced colitis. Am J Physiol Gastrointest Liver Physiol. 2003;284:G385–G391.

    PubMed  CAS  Google Scholar 

  7. Summers RW, Elliott DE, Urban JF Jr, Thompson R, Weinstock JV. Trichuris suis therapy in Crohn’s disease. Gut. 2005;54:87–90.

    Article  PubMed  CAS  Google Scholar 

  8. Summers RW, Elliott DE, Urban JF Jr, Thompson R, Weinstock JV. Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial. Gastroenterology. 2005;128:825–832.

    Article  PubMed  Google Scholar 

  9. Brown BN, Valentin JE, Stewart-Akers AM, McCabe GP, Badylak SF. Macrophage phenotype and remodeling outcomes in response to biologic scaffolds with and without a cellular component. Biomaterials. 2009;30:1482–1491.

    Article  PubMed  CAS  Google Scholar 

  10. Khan WI, Collins SM. Immune-mediated alteration in gut physiology and its role in host defence in nematode infection. Parasite Immunol. 2004;26:319–326.

    Article  PubMed  CAS  Google Scholar 

  11. Ruyssers NE, De Winter BY, De Man JG, et al. Therapeutic potential of helminth soluble proteins in TNBS-induced colitis in mice. Inflamm Bowel Dis. 2009;15:491–500.

    Article  PubMed  Google Scholar 

  12. Motomura Y, Wang H, Deng Y, El-Sharkawy RT, Verdu EF, Khan WI. Helminth antigen-based strategy to ameliorate inflammation in an experimental model of colitis. Clin Exp Immunol. 2009;155:88–95.

    Article  PubMed  CAS  Google Scholar 

  13. Yera H, Andiva S, Perret C, Limonne D, Boireau P, Dupouy-Camet J. Development and evaluation of a Western blot kit for diagnosis of human trichinellosis. Clin Diagn Lab Immunol. 2003;10:793–796.

    PubMed  Google Scholar 

  14. Smith P, Mangan NE, Walsh CM, et al. Infection with a helminth parasite prevents experimental colitis via a macrophage-mediated mechanism. J Immunol. 2007;178:4557–4566.

    PubMed  CAS  Google Scholar 

  15. Wendelsdorf K, Bassaganya-Riera J, Hontecillas R, Eubank S. Model of colonic inflammation: immune modulatory mechanisms in inflammatory bowel disease. J Theor Biol. 2010;264:1225–1239.

    Article  PubMed  CAS  Google Scholar 

  16. Nagano I, Wu Z, Takahashi Y. Species-specific antibody responses to the recombinant 53-kilodalton excretory and secretory proteins in mice infected with Trichinella spp. Clin Vaccine Immunol. 2008;15:468–473.

    Article  PubMed  CAS  Google Scholar 

  17. Bobin-Dubigeon C, Collin X, Grimaud N, Robert JM, Le Baut G, Petit JY. Effects of tumour necrosis factor-alpha synthesis inhibitors on rat trinitrobenzene sulphonic acid-induced chronic colitis. Eur J Pharmacol. 2001;431:103–110.

    Article  PubMed  CAS  Google Scholar 

  18. Hunter MM, Wang A, Hirota CL, McKay DM. Neutralizing anti-IL-10 antibody blocks the protective effect of tapeworm infection in a murine model of chemically induced colitis. J Immunol. 2005;174:7368–7375.

    PubMed  CAS  Google Scholar 

  19. Stewart GL, Wood BG, Boley RB. Modulation of host response by Trichinella pseudospiralis. Parasite Immunol. 1985;7:223–233.

    Article  PubMed  CAS  Google Scholar 

  20. Chakir H, Wang H, Lefebvre D, Webb J, Scott FW. T-bet/GATA-3 ratio as a measure of the Th1/Th2 cytokine profile in mixed cell populations: predominant role of GATA-3. J Immunol Methods. 2003;278:157–169.

    Article  PubMed  CAS  Google Scholar 

  21. Rengarajan J, Szabo S, Glimcher L. Transcriptional regulation of Th1/Th2 polarization. Immunol Today. 2000;21:479–483.

    Article  PubMed  CAS  Google Scholar 

  22. Deventer SJH. Tumor necrosis factor and Crohn’s disease. Gut. 1997;40:443–448.

    PubMed  Google Scholar 

  23. Elliott DE, Setiawan T, Metwali A, Blum A, Urban JF Jr, Weinstock JV. Heligmosomoides polygyrus inhibits established colitis in IL-10-deficient mice. Eur J Immunol. 2004;34:2690–2698.

    Article  PubMed  CAS  Google Scholar 

  24. Zurawski G, De Vries JE. Interleukin-13, an interleukin-4 like cytokine that acts on monocytes and B cells, but not on T-cells. Immunol Today. 1994;15:19–26.

    Article  PubMed  CAS  Google Scholar 

  25. Herbert DR, Hölscher C, Mohrs M, et al. Alternative macrophage activation is essential for survival during schistosomiasis and downmodulates T helper 1 responses and immunopathology. Immunity. 2004;20:623–635.

    Article  PubMed  CAS  Google Scholar 

  26. Persaud R, Wang A, Reardon C, McKay DM. Characterization of the immuno-regulatory response to the tapeworm Hymenolepis diminuta in the non-permissive mouse host. Int J Parasitol. 2007;37:393–403.

    Article  PubMed  CAS  Google Scholar 

  27. Hunter MM, Wang A, Parhar KS, et al. In vitro-derived alternatively activated macrophages reduce colonic inflammation in mice. Gastroenterology. 2010;138:1395–1405.

    Article  PubMed  CAS  Google Scholar 

  28. Witte MB, Barbul A. Arginine physiology and its implication for wound healing. Wound Repair Regen. 2003;11:419–423.

    Article  PubMed  Google Scholar 

  29. Anthony RM, Urban JF, Alem F, et al. Memory T(H)2 cells induce alternatively activated macrophages to mediate protection against nematode parasites. Nat Med. 2006;12:955–960.

    Article  PubMed  CAS  Google Scholar 

  30. Loke P, Gallagher I, Nair MG, et al. Alternative activation is an innate response to injury that requires CD4 + T cells to be sustained during chronic infection. J Immunol. 2007;179:3926–3936.

    PubMed  CAS  Google Scholar 

  31. Goodridge HS, Marshall FA, Else KJ, et al. Immunomodulation via novel use of TLR4 by the filarial nematode phosphorylcholine-containing secreted product, ES-62. J Immunol. 2005;174:284–293.

    PubMed  CAS  Google Scholar 

  32. Kane CM, Cervi L, Sun J, et al. Helminth antigens modulate TLR-initiated dendritic cell activation. J Immunol. 2004;173:7454–7461.

    PubMed  CAS  Google Scholar 

  33. Hunter MM, Wang A, McKay DM. Helminth infection enhances disease in a murine TH2 model of colitis. Gastroenterology. 2007;132:1320–1330.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the China National Great Basic Research Program (the 973 program, No. 2010CB530003) and the China National Natural Science Foundation (No. 30771887).

Author information

Authors and Affiliations

  1. Department of General Internal Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China

    Linlin Du, Hao Tang, Zhongfu Ma & Jia Xu

  2. Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China

    Wenchao Gao, Jiajia Chen, Wenjia Gan, Zhaoping Zhang, Xinbing Yu & Xuchu Hu

  3. Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China

    Xingwang Zhou

  4. 74 Zhongshan 2nd Road, Guangzhou, 510080, China

    Xuchu Hu

Authors
  1. Linlin Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hao Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhongfu Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jia Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wenchao Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jiajia Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Wenjia Gan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zhaoping Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xinbing Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Xingwang Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Xuchu Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xuchu Hu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Du, L., Tang, H., Ma, Z. et al. The Protective Effect of the Recombinant 53-kDa Protein of Trichinella spiralis on Experimental Colitis in Mice. Dig Dis Sci 56, 2810–2817 (2011). https://doi.org/10.1007/s10620-011-1689-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-011-1689-8

Keywords

Search

Navigation