title: Brugia malayi soluble and excretory-secretory proteins attenuate development of streptozotocin-induced type 1 diabetes in mice.
abstract: Understanding the modulation of the host-immune system by pathogens-like filarial parasites offers an alternate approach to prevent autoimmune diseases. In this study, we have shown that treatment with filarial proteins prior to or after the clinical onset of streptozotocin-induced type-1 diabetes (T1D) can ameliorate the severity of disease in BALB/c mice. Pre-treatment with Brugia malayi adult soluble (Bm A S) or microfilarial excretory-secretory (Bm mf ES) or microfilarial soluble (Bm mf S) antigens followed by induction of diabetes led to lowering of fasting blood glucose levels with as many as 57.5-62.5% of mice remaining nondiabetic. These proteins were more effective when they were used to treat the mice with established T1D as 62.5-71.5% of the mice turned to be nondiabetic. Histopathological examination of pancreas of treated mice showed minor inflammatory changes in pancreatic islet cell architecture. The therapeutic effect was found to be associated with the decreased production of cytokines TNF-α & IFN-γ and increased production of IL-10 in the culture supernatants of splenocytes of treated mice. A switch in the production of anti-insulin antibodies from IgG2a to IgG1 isotype was also seen. Together these results provide a proof towards utilizing the filarial derived proteins as novel anti-diabetic therapeutics.
authors.affiliation: Department of Biochemistry & JB Tropical Disease Research Institute, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Maharashtra, India.
authors.forename: N
authors.initials: N
authors.lastname: Amdare
authors.affiliation: Department of Biochemistry & JB Tropical Disease Research Institute, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Maharashtra, India.
authors.forename: V
authors.initials: V
authors.lastname: Khatri
authors.affiliation: Department of Biochemistry & JB Tropical Disease Research Institute, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Maharashtra, India.
authors.forename: R S P
authors.initials: RS
authors.lastname: Yadav
authors.affiliation: Department of Anatomy, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Maharashtra, India.
authors.forename: A
authors.initials: A
authors.lastname: Tarnekar
authors.affiliation: Department of Biochemistry & JB Tropical Disease Research Institute, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Maharashtra, India.
authors.forename: K
authors.initials: K
authors.lastname: Goswami
authors.affiliation: Department of Biochemistry & JB Tropical Disease Research Institute, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Maharashtra, India.
authors.forename: M V R
authors.initials: MV
authors.lastname: Reddy
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000627:therapeutic use; D017178:Brugia malayi / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D005260:Female; D015801:Helminth Proteins / Q000378:metabolism / Q000627:therapeutic use*; D006790:Host-Parasite Interactions; D007107:Immune System; D007074:Immunoglobulin G / Q000378:metabolism; D007515:Islets of Langerhans / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008842:Microfilariae; D013311:Streptozocin
chemical_list: D000947:Antigens, Helminth; D016207:Cytokines; D015801:Helminth Proteins; D007074:Immunoglobulin G; D013311:Streptozocin
keywords: Brugia malayi; adult soluble protein; microfilariae excretory-secretory protein; microfilariae soluble protein; therapeutic; type 1 diabetes