24Dec 2019

EVALUATION OF IMMUNOMODULATORY EFFECT OF FILARIAL ANTIGENS ON THE DEVELOPMENT OF TYPE I DIABETES

  • Assistant Professor, Department of Biochemistry, MGM Medical College Aurangabad
  • Deputy Medical Superitendent, WCL Pench Area, Chhindwara, Madhya Pradesh
Crossref Cited-by Linking logo
  • Abstract
  • Keywords
  • References
  • Cite This Article as
  • Corresponding Author

The rapid worldwide increase of this disease has challenged the researchers for explaining the rising trend in type 1 diabetes. Evidences are available in support of an inverse relationship between worm infection and T helper type 1/17 (Th1/17) - based inflammatory disorder such as Type 1 diabetes suggesting the immunomodulatory effect of helminth molecules in this condition. The objective of the study was to evaluate the immunomodulatory effect of filarial antigens (Bm mf\'s/ Bmmf\'ES\'/ rBmCys) on the development of type 1 diabetes. The mice were either pre-treated with or without the said proteins using alum as adjuvant (25 ?g) followed by experimental induction of diabetes for 2 months. The blood glucose level and pancreatic histopathological changes were measured. There was significant reduction in the glucose level in diabetic group of mice pre-treated separately with filarial native proteins (Bm mf\'s and Bmmf\'ES) compared to diabetic mice pre-treated with only Alum(p<0.002 andp<0.001). Almost 70% of the mice pre-treated with Bmmf\'ES showed recovery from diabetes at the end of the experiment period. Although all mice had evidence of ongoing pancreatic islet cell inflammation by histology, mice pre-treated with filarial proteins had greater numbers of total intact islets and non-infiltrated islets than untreated group of mice. These findings suggest that filarial derived proteins play pivotal role in the amelioration of disease condition in mice and act as novel immunomodulators in the treatment of type 1 diabetes.

  1. Aravindhan V, Mohan V, Surendar J. Decreased prevalence of lymphatic filariasis among diabetic subjects associated with a diminished pro-inflammatory cytokine response. PLoS Negl Trop Dis. 2010; 4: e707.
  2. Chenthamarakshan V, Reddy MVR, Harinath BC. Diagnostic potential of fractionated Brugia malayi microfilarial excretory-secretory antigen for bancroftian filariasis. Trans Roy Soc Trop Med & Hyg. 1996a; 90: 250- 254.
  3. Fleming JO and Cook TD. Multiple sclerosis and the hygiene hypothesis. NEUROLOGY. 2006; 67 (1-2): 2085-86.
  4. Harnett W,Harnett MM,?Byron O. Structural/functional aspects of ES-62-a secreted immunomodulatory phosphorylcholine-containing filarial nematode glycoprotein. Curr Protein Pept Sci.?2003; 4 (1): 59- 71.
  5. Harnett W, McInnes IB, Harnett MM. ES-62 a filarial nematode derived immuno-modulator with anti-inflammatory potential. Immunology Letters. 2004; 94 (1-2): 27- 33.
  6. Hartmann S, Kyewski B, Sonnenburg B, and Lucius R. A filarial cysteine protease inhibitor down-regulates T-cell proliferation and enhances interleukin-10 production. Eur. J. Immunol. 1997; 27: 2253? 2260.
  7. Hartmann S and Lucius R Modulation of host immune responses by nematode cystatins. Int. J. Parasitol. 2003; 33: 1291? 1302.
  8. Hubner MP, Stocker JT and Mitre E. 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. 2009; 127 (4): 512? 522.
  9. Imai S, Tezuka H, Furuhashi Y, Muto R, Fujita K. A factor of inducing IgE from a filarial parasite is an agonist of human CD40. J Biol Chem. 2001; 276(49): 46118- 24.
  10. Kaliraj P, Ghirnikar SN, Harinath BC. Fractionation and evaluation of Wuchereria bancrofti microfilarial antigens in immunodianosis of bancroftian filariasis. Ind J Exptl Biol. 1982; 20: 440- 444.
  11. Kullberg MC, Pearce EJ, Hieny SE, Sher A, Berzofsky JA. Infection with Schistosoma mansoni alters Th1/Th2 cytokine responses to a non-parasite antigen. J Immunol. 1992; 148: 3264? 70.
  12. La Flamme AC, Scott P, Pearce EJ. Schistosomiasis delays lesion resolution during Leishmania major infection by impairing parasite killing by macrophages. Parasite Immunol. 2002; 24: 339? 45.
  13. Maizels RM, Pearce EJ, Artis D, Yazdanbakhsh M and Wynn TA. Regulation of pathology and immunity in helminth infections. Journal of Experimental Medicine. 2009; 206: 2059- 2066.
  14. McInnes IB, Leung BP, Liew FY. A novel therapeutic approach targeting articular inflammation using the filarial nematode-derived phosphorylcholine-containing glycoprotein ES-62. Journal of Immunology. 2003; 171: 2127- 2133.
  15. Onkamo P, V??n?nen S,?? Karvonen? M,?? Tuomilehto? Worldwide increase in incidence of Type I diabetes ? the analysis of the data on published incidence trends. Diabetologia 1999; 42 (12): 1395- 1403.
  16. Patel SP, Jarvelin MR, Little MP. Systematic review of worldwide variations of the prevalence of wheezing symptoms in children. Environ Health. 2008; 7: 57.
  17. Ramachandran A, Snehalatha C, Krishnaswamy CV. The Incidence of IDDM in children in urban population in southern India. Diabetes Res Clin Pract. 1996; 34: 79- 82.
  18. Saunders KA, Raine T, Cooke A, Lawrence CE. Inhibition of autoimmune type 1 diabetes by gastrointestinal helminth infection. Infect Immun. 2007; 75: 397? 407.
  19. Schierack P, Lucius R, Sonnenburg B, Schilling K, Hartmann S. Parasite-specific immunomodulatory functions of filarial cystatin. Infect Immun. 2003; 71 (5): 2422- 9.
  20. Sewell DL, Reinke EK, Hogan LH, Sandor M, Fabry Z. Immunoregulation of CNS autoimmunity by helminth and mycobacterial infections. Immunol Lett. 2002; 82 (1-2):101- 10.
  21. Tisch R and McDevitt H. Insulin dependent Diabetes Mellitus. Cell. 1996; 85291- 297.
  22. Weinstock JV, Elliot DE. Helminths and the IBD hygiene hypothesis. Inflamm Bowel Dis. 2009; 15: 128- 33.
  23. Zaccone P, Fehervari Z, Jones FM, Sidobre S, Kronenberg M, Dunne DW, Cooke A. Schistosoma mansoni antigens modulate the activity of the innate immune response and prevent onset of type 1 diabetes. Eur. J. Immunol. 2003; 33: 1439? 1449.

[Manjusha Hivre and Sameer Khan (2019); EVALUATION OF IMMUNOMODULATORY EFFECT OF FILARIAL ANTIGENS ON THE DEVELOPMENT OF TYPE I DIABETES Int. J. of Adv. Res. 7 (Dec). 126-135] (ISSN 2320-5407). www.journalijar.com

Manjusha Hivre
Department of Biochemistry, MGM Medical College Aurangabad

DOI:

Article DOI: 10.21474/IJAR01/10136      
DOI URL: http://dx.doi.org/10.21474/IJAR01/10136

Download Full Paper

Download PDF No. of Downloads: 19 | No. of Views: 53