research focus

The main focus of the Lab is to study the altered immune responses at the interface of infectious diseases and metabolic disorders. Currently, the lab focuses on two important aspects of diabetic research namely

1. Inflammation and immunity under conditions of diabetes and infectious diseases co-morbidities,
2. Role of inflammation in diabetic complications

On-going projects

1. Immune response under conditions of diabetes and tuberculosis In 1993, WHO announced TB as a 'global emergency'. The increasing incidence of TB is mainly due to 'HIV-TB nexus' and increasing incidence of XDR/MDR-TB. Next to HIV, diabetes (DM) serves as a major risk factor for tuberculosis. Unfortunately, the 'DM-TB nexus' is not well understood. The consequences of these converging epidemics are likely to be substantial especially for India were TB as always been a major problem and the prevalence of diabetes is fast increasing. Several studies indicate that, patients with TB who have DM present a higher bacillary load in sputum, delayed mycobacterial clearance and higher rates of multidrug-resistant infections. These results imply that patients with TB who have DM may be more seriously ill and may pose higher risk for spreading TB in the community. Thus, these issues require urgent attention. Projects have been initiated in the lab to address the impact of diabetes on the 'protective immune correlates' of TB.
2. Immune system in diabetes and Lymphatic filariasis (LF) coexistence The 'Hygiene Hypothesis' was first put forth in 1989 by David P. Strachan in an article published in the British Medical Journal. It is used to explain the increase in the prevalence of allergies and autoimmunity in developed countries due to the decreasing prevalence of infectious agents. Infection with systemic helminths, in addition to causing morbidity on their own, may have an impact on co-morbidities by means of immunomodulation. Till date no study has addressed the incidence of LF among diabetic subjects. Studies carried out at our lab has shown decreased prevalence of LF among diabetic subjects (both type-1 and -2) compared to controls which was strongly associated with LF mediated immunomodulation. We think, apart from allergies and autoimmunity the hygiene hypothesis has to be extended to metabolic diseases like diabetes ('extended hygiene hypothesis'). We think the decreasing prevalence of LF in India due to mass drug administration might have an effect on the increasing prevalence of both type-1 and -2 diabetes. Further, these findings might have great implications for future helminth based vaccines/therapeutics against diabetes.
3. Role of inflammation in Diabetic nephropathy and metabolic syndrome. Metabolic syndrome (MS) is a term used to refer to a conglomeration of metabolic disorders including abdominal obesity, hypertriglyceridemia, low HDL cholesterol (HDL-C), hypertension and insulin resistance. MS is associated with a two fold risk for cardiovascular disease and a 5 fold risk for diabetes. Due to sedentary lifestyle and escalation of obesity rates, the prevalence of the MS is increasing worldwide. In India, the prevalence rate of MS is 30% which is higher than that reported for other Asian and European countries. Inflammation has been identified as one of the major etiological factors for MS. The inflammation in MS is chronic, low grade and non-antigen specific in nature and is associated with insulin resistance. The organ specific (adipose) inflammation, seen during early stages of the disease, becomes more systemic with disease progression and starts affecting the blood vessels leading to vasculopathies like kidney and heart failures, which are commonly seen in MS. Studies conducted at our lab has shown that, with increasing risk factors for MS, there was a serial increase in TGF-beta and decrease in IL-17 levels in the serum. Further, subjects with MS showed a typical mixed Th-1-Th-2 response which we think might make them more susceptible for diseases like TB. Experiments are under way to study the role of Toll-like receptors in MS and diabetic nephropathy.