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Therapeutic potential of the immunomodulatory proteins Wuchereria bancrofti L2 and Brugia malayi abundant larval transcript 2 against streptozotocin-induced type 1 diabetes in mice

Published online by Cambridge University Press:  26 September 2016

N.P. Amdare ,
V.K. Khatri ,
R.S.P. Yadav ,
A. Tarnekar ,
K. Goswami  and
M.V.R. Reddy
N.P. Amdare
Affiliation:
Department of Biochemistry and JB Tropical Disease Research Centre, Mahatma Gandhi Institute of Medical Sciences, Sevagram-442 102, Maharashtra, India
V.K. Khatri
Affiliation:
Department of Biochemistry and JB Tropical Disease Research Centre, Mahatma Gandhi Institute of Medical Sciences, Sevagram-442 102, Maharashtra, India
R.S.P. Yadav
Affiliation:
Department of Biochemistry and JB Tropical Disease Research Centre, Mahatma Gandhi Institute of Medical Sciences, Sevagram-442 102, Maharashtra, India
A. Tarnekar
Affiliation:
Department of Anatomy, Mahatma Gandhi Institute of Medical Sciences, Sevagram-442 102, Maharashtra, India
K. Goswami
Affiliation:
Department of Biochemistry and JB Tropical Disease Research Centre, Mahatma Gandhi Institute of Medical Sciences, Sevagram-442 102, Maharashtra, India
M.V.R. Reddy*
Affiliation:
Department of Biochemistry and JB Tropical Disease Research Centre, Mahatma Gandhi Institute of Medical Sciences, Sevagram-442 102, Maharashtra, India
*
*Fax: +917152-284038 E-mail: reddymvr@gmail.com
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Abstract

Epidemiological and experimental evidence has supported the concept of using helminths as alternative bio-therapeutic agents in the treatment of type 1 diabetes (T1D). In the current study, two filarial proteins, recombinant Wuchereria bancrofti L2 (rWbL2) and Brugia malayi abundant larval transcript 2 (rBmALT-2) have been investigated, individually and in combination, for their therapeutic potential in streptozotocin (STZ)-induced T1D. The rWbL2 and rBmALT-2 proteins, when administered individually or in combination, have resulted in lowering of the blood glucose levels and reducing the incidence of T1D in mice. In addition, these proteins have led to reduced lymphocytic infiltration and decreased islet damage and inflammation. The curative effect was found to be associated with the suppression of release of tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), and increased production of interleukin (IL)-4, IL-5 and IL-10 cytokines by the splenocytes of the diabetic mice. Insulin-specific IgG1 and antigen-specific IgE antibodies were found to be elevated in the sera of mice treated with rWbL2 and rBmALT-2 proteins. From the findings in this study, it can be envisaged that both of these filarial immunomodulatory proteins have the potential to ameliorate T1D by altering the regulatory immune responses.

Type
Research Papers
Information
Journal of Helminthology , Volume 91 , Issue 5 , September 2017 , pp. 539 - 548
Copyright
Copyright © Cambridge University Press 2016 

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References

Adjobimey, T. & Hoerauf, A. (2010) Induction of immunoglobulin G4 in human filariasis: an indicator of immunoregulation. Annals of Tropical Medicine and Parasitology 104, 455–464.Google Scholar
Alexandra, K.K., Müller, C. & Vollmar, A.M. (2002) Inhibition of LPS-induced nitric oxide and TNF alpha production by alpha-lipoic acid in rat Kupffer cells and in RAW 264.7 murine macrophages. Immunology and Cell Bioolgy 80, 550–557.Google Scholar
Alison, B.E. (2014) Treatment of mild hypoglycemia. Diabetes Spectrum 27, 8–62.Google Scholar
Amdare, N., Khatri, V., Yadav, R.S.P., Tarnekar, A., Goswami, K. & Reddy, M.V.R. (2015) Brugia malayi soluble and excretory-secretory proteins attenuate development of streptozotocin-induced type 1 diabetes in mice. Parasite Immunology 37, 624–634.Google Scholar
Bashi, T., Bizzaro, G., Shor, D.B.A., Blank, M. & Shoenfeld, Y. (2015) The mechanisms behind helminth's immunomodulation in autoimmunity. Autoimmunity Reviews 14, 98–104.Google Scholar
Boitelle, A., Di Lorenzo, C., Scales, H.E., Devaney, E., Kennedy, M.W., Garside, P. & Lawrence, C.E. (2005) Contrasting effects of acute and chronic gastro-intestinal helminth infections on a heterologous immune response in a transgenic adoptive transfer model. International Journal for Parasitology 35, 765–775.Google Scholar
Callewaert, H.I., Gysemans, C.A., Ladrière, L., D'Hertog, W., Hagenbrock, J., Overbergh, L., Eizirik, D.L. & Mathieu, C. (2007) Deletion of STAT-1 pancreatic islets protects against streptozotocin-induced diabetes and early graft failure but not against late rejection. Diabetes 56, 2169–2173.Google Scholar
Cooke, A., Tonks, P., Jones, F.M., O'Shea, H., Hutchings, P. & Fulford, A.J. (1999) Infection with Schistosoma mansoni prevents insulin dependent diabetes mellitus in non-obese diabetic mice. Parasite Immunology 21, 169–176.Google Scholar
Decker, K. (1990) Biologically active products of stimulated liver macrophages (Kupffer cells). European Journal of Biochemistry 192, 245–261.CrossRefGoogle ScholarPubMed
Denis, M.C., Mahmood, U., Benoist, C., Mathis, D. & Weissleder, R. (2004) Imaging inflammation of the pancreatic islets in type 1 diabetes. Proceedings of the National Academy of Sciences, USA 101, 12634–12639.Google Scholar
El-Wakil, H.S., Aboushousha, T.S., El Haddad, O., Gamil, N.B., Mansour, T. & El-Said, H. (2002) Effect of Schistosoma mansoni egg deposition on multiple low dose streptozotocin induced insulin dependent diabetes. Journal of the Egyptian Society of Parasitology 32, 987–1002.Google ScholarPubMed
Esensten, J.H., Lee, M.R., Glimcher, L.H. & Bluestone, J.A. (2009) T-bet deficient NOD mice are protected from diabetes due to defects in both T cell and innate immune system function. Journal of Immunology 183, 75–82.Google Scholar
Espinoza-Jiménez, A., Rivera-Montoya, I., C'ardenas-Arreola, R., Moran, L. & Terrazas, L.I. (2010) Taenia crassiceps infection attenuates multiple low-dose streptozotocin-induced diabetes. BioMed Research International 2010, 1–11.Google Scholar
Flohr, C., Quinnell, R.J. & Britton, J. (2009) Do helminth parasites protect against atopy and allergic disease? Clinical & Experimental Allergy 39, 20–32.CrossRefGoogle ScholarPubMed
Gillan, V., Lawrence, R.A. & Devaney, E. (2005) B cells play a regulatory role in mice infected with the l3 of Brugia pahangi . International Immunology 17, 373–382.Google Scholar
Gnanasekar, M., Rao, K. & He, Y. (2004) Novel phage display-based subtractive screening to identify vaccine candidates of Brugia malayi . Infection & Immunity 72, 4707–4715.CrossRefGoogle ScholarPubMed
Gomez-Escobar, N., Bennett, C., Prieto-Lafuente, L., Aebischer, T., Blackburn, C. & Maizels, R.M. (2005) Heterologous expression of the filarial nematode alt gene products reveals their potential to inhibit immune function. BMC Biology 3, 1.Google Scholar
Hubner, M.P., Stoker, J.T. & Mitre, E. (2009) Inhibition of type 1 diabetes in filaria-infected non-obese diabetic mice is associated with a T helper type 2 shift and induction of FoxP3+ regulatory T cells. Immunology 127, 512–522.Google Scholar
Hussain, S. & Delovitch, T.L. (2007) Intravenous transfusion of BCR-activated B cells protects NOD mice from type 1 diabetes in an IL-10-dependent manner. Journal of Immunology 179, 7225–7232.CrossRefGoogle Scholar
Imai, S., Tezuka, H. & Fujita, K. (2001) A factor of inducing IgE from a filarial parasite prevents insulin-dependent diabetes mellitus in non-obese diabetic mice. Biochemical and Biophysical Research Communications 286, 1051–1058.Google Scholar
Li, M., Song, L.J. & Qin, X. (2014) Advances in the cellular immunological pathogenesis of type 1 diabetes. Journal of Cellular and Molecular Medicine 18, 749–758.Google Scholar
Liu, Q., Saunders, K., Mishra, P.K., Mousavi, G., Liu, Z. & Gaydo, A. (2009) Helminth infection can reduce insulitis and type 1 diabetes through CD25- and IL-10-independent mechanisms. Infection and Immunity 77, 5347–5358.Google Scholar
Lund, M.E., O'Brien, B.A., Hutchinson, A.T., Robinson, M.W., Simpson, A.M., Dalton, J.P. & Donnelly, S. (2014) Secreted proteins from the helminth Fasciola hepatica inhibit the initiation of autoreactive T cell responses and prevent diabetes in the NOD mouse. PLoS One 9, e86289.CrossRefGoogle ScholarPubMed
Madhumathi, J., Prince, P.R., Nageswara, R.D. & Kaliraj, P. (2010) Dominant T-cell epitopes of filarial BmALT-2 and their cytokine profile in BALB/c mice. Parasite Immunology 32, 760–763.Google Scholar
Maizels, M. (2009) Parasite immunomodulation and polymorphisms of the immune system. Journal of Biology 8, 62–65.Google Scholar
Malyala, P. & Singh, M. (2008) Endotoxin limits in formulations for preclinical research. Journal of Pharmaceutical Sciences 97, 2041–2044.Google Scholar
McSorley, H.J. & Maizels, R.M. (2012) Helminth infections and host immune regulation. Clinical Microbiology Reviews 25, 585–608.Google Scholar
Mishra, P.K., Patel, N., Wu, W., Bleich, D. & Gause, W.C. (2013) Prevention of type 1 diabetes through infection with an intestinal nematode parasite requires IL-10 in the absence of a Th2-type response. Mucosal Immunology 6, 297–308.Google Scholar
Moller, M., Gravenor, B., Roberts, E., Sun, D., Gao, P. & Hopkin, M. (2007) Genetic haplotypes of Th-2 immune signalling link allergy to enhanced protection to parasitic worms. Human Molecular Genetics 16, 1828–1836.CrossRefGoogle ScholarPubMed
Muller, A., Schott-Ohly, P., Dohle, C. & Gleichmann, H. (2002) Differential regulation of Th1-type and Th2-type cytokine profiles in pancreatic islets of C57BL/6 and BALB/c mice by multiple low doses of streptozotocin. Immunobiology 205, 35–50.Google Scholar
Osada, Y. & Kanazawa, T. (2010) Parasitic helminths: new weapons against immunological disorders. Journal of Biomedicine and Biotechnology 2010, 743–758.Google Scholar
Osada, Y., Yamada, S., Nabeshima, A., Yamagishi, Y., Ishiwata, K., Nakae, S. & Kanazawa, T. (2013) Heligmosomoides polygyrus infection reduces severity of type 1 diabetes induced by multiple low-dose streptozotocin in mice via STAT6- and IL-10-independent mechanisms. Experimental Parasitology 135, 388–396.Google Scholar
Pescovitz, M.D., Greenbaum, C.J., Krause-Steinrauf, H., Becker, D.J., Gitelman, S.E., Goland, R. & Raskin, P. (2009) Rituximab, B-lymphocyte depletion, and preservation of beta-cell function. New England Journal of Medicine 361, 2143–2152.Google Scholar
Pinkse, G., Tysma, O. & Bergen, C. (2005) Autoreactive CD8 T cells associated with cell destruction in type 1 diabetes. Proceedings of the National Academy of Sciences,USA 102, 18425–18430.Google Scholar
Reddy, S.M., Reddy, P.S., Amdare, N., Khatri, V., Tarnekar, A., Goswami, K. & Reddy, M.V.R. (2016) Filarial abundant larval transcript protein ALT-2: an immunomodulatory therapeutic agent for type 1 diabetes. Indian Journal of Clinical Biochemistry. doi: 10.1007/s12291-016-0572-y.Google Scholar
Santos-Junior, R.R., Sartori, A. & Lima, D.S. (2009) DNA vaccine containing the mycobacterial hsp65 gene prevented insulitis in MLD–STZ diabetes. Journal of Immune Based Vaccines 7, 4.CrossRefGoogle Scholar
Saunders, K.A., Raine, T., Cooke, A. & Lawrence, C.E. (2007) Inhibition of autoimmune type 1 diabetes by gastrointestinal helminth infection. Infection and Immunity 75, 397–407.Google Scholar
Strachan, D.P. (1989) Hay fever, hygiene, and household size. British Medical Journal 299, 1259–1260.Google Scholar
Taira, J., Ohminea, W., Nanbub, H. & Uedab, K. (2013) Inhibition of LPS-stimulated NO production in RAW264.7 macrophages throμgh iNOS suppression and nitrogen radical scavenging by phenolic compounds from Agrimonia pilosa Ledeb. Oxidants and Antioxidants in Medical Science 2, 21–28.Google Scholar
Tisch, R. & McDevitt, H. (1996) Insulin dependent diabetes mellitus. Cell 85, 291–297.Google Scholar
Von Mutius, E. (2007) Allergies, infections and the hygiene hypothesis – the epidemiological evidence. Immunobiology 212, 433–439.Google Scholar
Wilson, D.M. & Buckingham, B. (2001) Prevention of type 1a diabetes mellitus. Paediatrics Diabetes 2, 17–24.Google Scholar
Wilson, M.S., Taylor, M.D., O'Gorman, M.T., Balic, A. & Barr, T.A. (2010) Helminth-induced CD19+CD23hi B cells modulate experimental allergic and autoimmune inflammation. European Journal of Immunology 40, 1682–1696.Google Scholar
Yoon, J.W. & Jun, H.S. (2005) Autoimmune destruction of pancreatic β cells. American Journal of Therapy 12, 580–591.Google Scholar
Zaccone, P. & Hall, S. (2012) Helminth infection and type 1 diabetes. Review of Diabetic Studies 9, 272–286.Google Scholar
Zaccone, P., Fehérvári, Z., Jones, F.M., Sidobre, S., Kronenberg, M., Dunne, D.W. & Cooke, A. (2003) Schistosoma mansoni antigens modulate the activity of the innate immune response and prevent onset of type 1 diabetes. European Journal of Immunology 33, 1439–1449.Google Scholar
Zaccone, P., Burton, O., Miller, N., Jones, F.M., Dunne, D.W. & Cooke, A. (2009) Schistosoma mansoni egg antigens induce Treg that participate in diabetes prevention in NOD mice. European Journal of Immunology 39, 1098–1107.Google Scholar
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