Filarial Abundant Larval Transcript Protein ALT-2: An Immunomodulatory Therapeutic Agent for Type 1 Diabetes.
Type 1 diabetes (T1D) that accounts for about 5-10 % of all diabetes cases results from the autoimmune destruction of the insulin-producing beta cells in the pancreas. It is characterized by severe inflammatory reaction mediated by pronounced T helper type-1 response. Parasitic infections having the ability to skew the host immune responses towards type-2 type as a part of their defense mechanism are able to induce protection against autoimmune diseases like T1D. Hence, the present study is undertaken to explore a recombinant abundant larval transcript protein of the human lymphatic filarial parasiteBrugia malayi(rBmALT-2), a known anti-inflammatory molecule for its therapeutic effect on streptozotocin (STZ)-induced T1D in mice. The diabetic mice on treatment with rBmALT-2 showed a significant (p< 0.0005) decrease in their fasting blood glucose levels. By the end of the second week after the initiation of treatment with the rBmALT-2, 28 % of the diabetic mice became normal and none of them were diabetic by the end of 5th week. The anti-diabetic effect of rBmALT-2 significantly correlated with the concomitant redressal of the pancreatic histopathological damage caused by STZ assault (rho = 0.87;p< 0.0005). The sera of rBmALT-2 treated diabetic mice had increased levels of IgG1 antibodies associated with decreased IgG2a antibodies against the principal autoantigen insulin. The splenocyte proliferative response and the cytokine release in the treated mice showed marked bias against inflammation skewing the immune response to Th-2 type. From this study, it can be envisaged that that filarial proteins like rBmALT-2 with effective immunomodulatory activity and anti-diabetic effect are promising alternative therapeutic agents for T1D.
Department of Biochemistry and JB Tropical Disease Research Centre, Mahatma Gandhi Institute of Medical Sciences, Sevagram, MS 442102 India.
Sridhar M
0000-0003-0838-9439
SM
Reddy
Department of Pharmacology, Sri Aurobindo Institute of Medical Sciences, Indore, MP 453555 India.
Pooja M
PM
Reddy
Department of Biochemistry and JB Tropical Disease Research Centre, Mahatma Gandhi Institute of Medical Sciences, Sevagram, MS 442102 India.
Nitin
N
Amdare
Department of Biochemistry and JB Tropical Disease Research Centre, Mahatma Gandhi Institute of Medical Sciences, Sevagram, MS 442102 India.
Vishal
V
Khatri
Department of Anatomy, Mahatma Gandhi Institute of Medical Sciences, Sevagram, MS 442102 India.
Aaditya
A
Tarnekar
Department of Biochemistry and JB Tropical Disease Research Centre, Mahatma Gandhi Institute of Medical Sciences, Sevagram, MS 442102 India.
Kalyan
K
Goswami
Department of Biochemistry and JB Tropical Disease Research Centre, Mahatma Gandhi Institute of Medical Sciences, Sevagram, MS 442102 India.
Maryada Venkata Rami
MVR
Reddy
Abundant larval transcript-2; Autoimmune diseases; Immunomodulators; Streptozotocin; Therapeutic; Type 1 diabetes