Indian Journal of Clinical Biochemistry

, Volume 33, Issue 3, pp 282–289 | Cite as

SXP–RAL Family Filarial Protein, rWbL2, Prevents Development of DSS-Induced Acute Ulcerative Colitis

  • Namdev S. Togre
  • Priyanka S. Bhoj
  • Vishal K. Khatri
  • Aditya Tarnekar
  • Kalyan GoswamiEmail author
  • Moreshwar R. Shende
  • M. V. R. Reddy
Original Article


Helminthic infections lead to the release of various molecules which play an important role in modulation of the host immune system. Such filarial proteins with immunomodulatory potential can be used for therapeutic purpose in inflammatory and immune mediated diseases. In the present study, we have explored the prophylactic effect of filarial SXP–RAL family protein of Wuchereria bancrofti i.e. rWbL2 protein in DSS induced inflammatory ulcerative colitis in a mouse model. Prior treatment of rWbL2, followed by induction of colitis, showed significantly reduced disease severity as indicated by the decreased disease manifestations and improved macroscopic and microscopic inflammation. This preventive effect was found to be associated with increased release of anti-inflammatory cytokine IL-10 and decreased release of proinflammatory cytokines IFN-γ, TNF-α, IL-6 and IL-17 by the splenocytes of treated mice. From this study, it can be envisaged that pretreatment with filarial protein, rWbL2, can prevent the establishment of ulcerative colitis in BALB/c mice. The underlying immunological mechanism may involve the up-regulation of Th2 immune response with down-regulation of Th1 response.


Helminths Ulcerative colitis Recombinant WbL2 Dextran sodium sulfate 



All authors gratefully acknowledge the financial assistance given by Department of Science and Technology (DST) and Department of Biotechnology (DBT), Ministry of Science & Technology, Government of India. Namdev Togre would like to thank Dr. Babasaheb Ambedkar Research and Training Institute (BARTI), Pune, Government of Maharashtra for fellowship.

Funding was provide by Department of Biotechnology , Ministry of Science and Technology (Grant No. BT/PR4988/INF/22/155/2012, dated 01/06/12)

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.


  1. 1.
    Carter MJ, Lobo AJ, Travis SP. Guidelines for the management of inflammatory bowel disease in adults. Gut. 2004;53(5):v1-6.Google Scholar
  2. 2.
    Goh KL, Xiao SD. Inflammatory bowel disease: a survey of the epidemiology in Asia. J Dig Dis. 2009;10(1):1–6.CrossRefPubMedGoogle Scholar
  3. 3.
    Cosnes J, Gower-Rousseau C, Seksik P, Cortot A. Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology. 2011;140(6):1785–94.CrossRefPubMedGoogle Scholar
  4. 4.
    Karlinger K, Györke T, Makö E, Mester Á, Tarján Z. The epidemiology and the pathogenesis of inflammatory bowel disease. Eur J Radiol. 2000;35(3):154–67.CrossRefPubMedGoogle Scholar
  5. 5.
    Björkstén B. Diverse microbial exposure–consequences for vaccine development. Vaccine. 2012;30(29):4336–40.CrossRefPubMedGoogle Scholar
  6. 6.
    Heylen M, Ruyssers NE, Joris G, Timmermans JP, Pelckmans PA, Moreels TG, et al. Worm proteins of Schistosoma mansoni reduce the severity of experimental chronic colitis in mice by suppressing colonic proinflammatory immune responses. PLoS ONE. 2014;9(10):e110002.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Hübner MP, Killoran KE, Rajnik M, Wilson S, Yim KC, Torrero MN, et al. Chronic helminth infection does not exacerbate mycobacterium tuberculosis infection. PLoS Negl Trop Dis. 2012;6(12):e1970.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Pineda MA, Al-Riyami L, Harnett W, Harnett MM. Lessons from helminth infections: ES-62 highlights new interventional approaches in rheumatoid arthritis. Clin Exp Immunol. 2014;177(1):13–23.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Büning J, Homann N, von Smolinski D, Borcherding F, Noack F, Stolte M, et al. Helminths as governors of inflammatory bowel disease. Gut. 2008;57(8):1182–3.CrossRefPubMedGoogle Scholar
  10. 10.
    Broadhurst MJ, Leung JM, Kashyap V, McCune JM, Mahadevan U, McKerrow JH. IL-22 + CD4 + T cells are associated with therapeutic trichuris trichiura infection in an ulcerative colitis patient. Sci Trans Med. 2010;2(60):60ra88.CrossRefGoogle Scholar
  11. 11.
    Jang SW, Cho MK, Park MK, Kang S, Na BK, Ahn SC, et al. Parasitic helminth cystatin inhibits DSS-induced intestinal inflammation via IL-10 + F4/80 + macrophage recruitment. Korean J Parasitol. 2011;49(3):245–54.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Rao KV, Eswaran M, Ravi V, Gnanasekhar B, Narayanan RB, Kaliraj P, et al. The Wuchereria bancrofti orthologue of Brugia malayi SXP1 and the diagnosis of bancroftian filariasis. Mol Biochem Parasitol. 2000;107(1):71–80.CrossRefPubMedGoogle Scholar
  13. 13.
    Adjobimey T, Hoerauf A. Induction of immunoglobulin G4 in human filariasis: an indicator of immunoregulation. Ann Trop Med Parasitol. 2010;104(6):455–64.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Amdare NP, Khatri VK, Yadav RS, Tarnekar A, Goswami K, Reddy MV. 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. 2016;2016:1–10.Google Scholar
  15. 15.
    Malyala P, Singh M. Endotoxin limits in formulations for preclinical research. J Pharm Sci. 2008;97(6):2041–4.CrossRefPubMedGoogle Scholar
  16. 16.
    Okayasu I, Hatakeyama S, Yamada M, Ohkusa T, Inagaki Y, Nakaya R. A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology. 1990;98(3):694–702.CrossRefPubMedGoogle Scholar
  17. 17.
    Khatri V, Amdare N, Tarnekar A, Goswami K, Reddy MV. Brugia malayi cystatin therapeutically ameliorates dextran sulfate sodium-induced colitis in mice. J Dig Dis. 2015;16(10):585–94.CrossRefPubMedGoogle Scholar
  18. 18.
    Dutra RC, Claudino RF, Bento AF, Marcon R, Schmidt ÉC, Bouzon ZL, et al. Preventive and therapeutic euphol treatment attenuates experimental colitis in mice. PLoS ONE. 2011;6(11):e27122.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Ruyssers NE, De Winter BY, De Man JG, Loukas A, Pearson MS, Weinstock JV, et al. Therapeutic potential of helminth soluble proteins in TNBS-induced colitis in mice. Inflamm Bowel Dis. 2009;15(4):491–500.CrossRefPubMedGoogle Scholar
  20. 20.
    Dieleman LA, Heizer WD. Nutritional issues in inflammatory bowel disease. Gastroenterol Clin N Am. 1998;27(2):435–51.CrossRefGoogle Scholar
  21. 21.
    Moreels TG, Joris G, Bogers JJ, De Winter BY, Vrolix G, Herman AG, et al. Effect of Schistosoma mansoni-induced granulomatous inflammation on murine gastrointestinal motility. Am J Physiol Gastrointest Liver Physiol. 2001;280(5):G1030–42.CrossRefPubMedGoogle Scholar
  22. 22.
    Schönemeyer A, Lucius R, Sonnenburg B, Brattig N, Sabat R, Schilling K, et al. Modulation of human T cell responses and macrophage functions by onchocystatin, a secreted protein of the filarial nematode Onchocerca volvulus. J Immunol. 2001;167(6):3207–15.CrossRefPubMedGoogle Scholar
  23. 23.
    Flohr C, Quinnell RJ, Britton J. Do helminth parasites protect against atopy and allergic disease? Clin Exp Allergy. 2009;39(1):20–32.CrossRefPubMedGoogle Scholar
  24. 24.
    Erb KJ. Can helminths or helminth-derived products be used in humans to prevent or treat allergic diseases? Trends Immunol. 2009;30(2):75–82.CrossRefPubMedGoogle Scholar
  25. 25.
    van Riet E, Hartgers FC, Yazdanbakhsh M. Chronic helminth infections induce immunomodulation: consequences and mechanisms. Immunobiology. 2007;212(6):475–90.CrossRefPubMedGoogle Scholar
  26. 26.
    Murai M, Turovskaya O, Kim G, Madan R, Karp CL, Cheroutre H, et al. Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis. Nat Immunol. 2009;10(11):1178–84.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Elson CO, Sartor RB, Tennyson GS, Riddell RH. Experimental models of inflammatory bowel disease. Gastroenterology. 1995;109(4):1344–67.CrossRefPubMedGoogle Scholar
  28. 28.
    Kim KA, Gu W, Lee IA, Joh EH, Kim DH. High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway. PLoS ONE. 2012;7(10):e47713.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Thirugnanam S, Pandiaraja P, Ramaswamy K, Murugan V, Gnanasekar M, Nandakumar K, et al. Brugia malayi: comparison of protective immune responses induced by Bm-alt-2 DNA, recombinant Bm-ALT-2 protein and prime-boost vaccine regimens in a jird model. Exp Parasitol. 2007;116(4):483–91.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Smith P, Mangan NE, Walsh CM, Fallon RE, McKenzie AN, van Rooijen N, et al. Infection with a helminth parasite prevents experimental colitis via a macrophage-mediated mechanism. J Immunol. 2007;178(7):4557–66.CrossRefPubMedGoogle Scholar
  31. 31.
    Alex P, Zachos NC, Nguyen T, Gonzales L, Chen TE, Conklin LS, et al. Distinct cytokine patterns identified from multiplex profiles of murine DSS and TNBS-induced colitis. Inflamm Bowel Dis. 2009;15(3):341–52.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Yang X, Yang Y, Wang Y, Zhan B, Gu Y, Cheng Y, et al. Excretory/secretory products from Trichinella spiralis adult worms ameliorate DSS-induced colitis in mice. PLoS ONE. 2014;9(5):e96454.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Wang S, Xie Y, Yang X, Wang X, Yan K, Zhong Z, et al. Therapeutic potential of recombinant cystatin from Schistosoma japonicum in TNBS-induced experimental colitis of mice. Parasit Vectors. 2016;9(1):6.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Du L, Tang H, Ma Z, Xu J, Gao W, Chen J, et al. The protective effect of the recombinant 53-kDa protein of Trichinella spiralis on experimental colitis in mice. Dig Dis Sci. 2011;56(10):2810–7.CrossRefPubMedGoogle Scholar
  35. 35.
    Cho MK, Lee CH, Yu HS. Amelioration of intestinal colitis by macrophage migration inhibitory factor isolated from intestinal parasites through Toll-like receptor 2. Parasit Immunol. 2011;33(5):265–75.CrossRefGoogle Scholar

Copyright information

© Association of Clinical Biochemists of India 2017

Authors and Affiliations

  • Namdev S. Togre
    • 1
  • Priyanka S. Bhoj
    • 1
  • Vishal K. Khatri
    • 1
  • Aditya Tarnekar
    • 2
  • Kalyan Goswami
    • 1
    Email author
  • Moreshwar R. Shende
    • 2
  • M. V. R. Reddy
    • 1
  1. 1.Department of Biochemistry, JB Tropical Disease Research CentreMahatma Gandhi Institute of Medical SciencesSevagramIndia
  2. 2.Department of AnatomyMahatma Gandhi Institute of Medical SciencesSevagramIndia

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