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Sreejit G.,DNA Diagnostics Center | Ahmed A.,DNA Diagnostics Center | Parveen N.,DNA Diagnostics Center | Jha V.,DNA Diagnostics Center | And 3 more authors.
PLoS Pathogens | Year: 2014

ESAT-6, an abundantly secreted protein of Mycobacterium tuberculosis (M. tuberculosis) is an important virulence factor, inactivation of which leads to reduced virulence of M. tuberculosis. ESAT-6 alone, or in complex with its chaperone CFP-10 (ESAT-6:CFP-10), is known to modulate host immune responses; however, the detailed mechanisms are not well understood. The structure of ESAT-6 or ESAT-6:CFP-10 complex does not suggest presence of enzymatic or DNA-binding activities. Therefore, we hypothesized that the crucial role played by ESAT-6 in the virulence of mycobacteria could be due to its interaction with some host cellular factors. Using a yeast two-hybrid screening, we identified that ESAT-6 interacts with the host protein beta-2-microglobulin (β2M), which was further confirmed by other assays, like GST pull down, co-immunoprecipitation and surface plasmon resonance. The C-terminal six amino acid residues (90–95) of ESAT-6 were found to be essential for this interaction. ESAT-6, in complex with CFP-10, also interacts with β2M. We found that ESAT-6/ESAT-6:CFP-10 can enter into the endoplasmic reticulum where it sequesters β2M to inhibit cell surface expression of MHC-I-β2M complexes, resulting in downregulation of class I-mediated antigen presentation. Interestingly, the ESAT-6:β2M complex could be detected in pleural biopsies of individuals suffering from pleural tuberculosis. Our data highlight a novel mechanism by which M. tuberculosis may undermine the host adaptive immune responses to establish a successful infection. Identification of such novel interactions may help us in designing small molecule inhibitors as well as effective vaccine design against tuberculosis. © 2014 Sreejit et al. Source


Parasannanavar D.J.,National Institute of Nutrition ICMR | Rajadhyaksha A.,King Edward Memorial Hospital | Ghosh K.,National Institute of Immunohaematology ICMR
Autoimmune Diseases | Year: 2014

Seronegative spondyloarthritis (SpA) are variably associated with HLA-B*27 antigen. HLA-B*27 negative SpA has also been reported from different parts of the world. There is paucity of data on this entity from Indian subcontinent. We studied 100 consecutively diagnosed HLA-B27 negative spondyloarthritis patients from a tertiary care center in India. Modified New York Criteria for ankylosing spondylitis (AS) and ESSG criteria for SpA were used for diagnosing patients. HLA-B*27 typing was done by an in-house PCR-SSP technique in SpA patients to exclude B*27 positive patients and PCR-SSOP technique was used to type 100 B*27 negative SpA patients and 100 controls from the same ethnicity. Frequency of B*07 was significantly increased (B*07: % PF 54 versus 18; OR 5.348; 95% CI 2.808-10.186; P value 1.14E - 07), whereas frequency of B*40 was significantly decreased (B*40: % PF 17 versus 32; OR 0.435; 95% CI 0.222-0.850; P value 0.013) when compared with B*27 negative controls. Among 100 SpA patients, 47 were undifferentiated spondyloarthritis and 33 patients were reactive arthritis patients. 40% of the patients were suffering from polyarticular arthritis, 35% had pauciarticular arthritis with knee joint, hip joint, ankle joint, and SI joint involvement. We conclude that B*07 was significantly associated with B27 negative spondyloarthropathy from Western India and majority of B*27 negative patients were uSpA. © 2014 Devaraj J. Parasannanavar et al. Source


Jeyakumar S.M.,National Institute of Nutrition ICMR | Vajreswari A.,National Institute of Nutrition ICMR
Indian Journal of Medical Research, Supplement | Year: 2015

During the last century, vitamin A has evolved from its classical role as a fat-soluble vitamin and attained the status of para-/autocrine hormone. Besides its well-established role in embryogenesis, growth and development, reproduction and vision, vitamin A has also been implicated in several other physiological processes. Emerging experimental evidences emphasize adipose tissue as an active endocrine organ with great propensity to continuous growth (throughout life). Due to various genetic and lifestyle factors, excess energy accumulates in adipose tissue as fat, resulting in obesity and other complications such as type 2 diabetes, hypertension, and cardiovascular disease. Recent in vitro and in vivo studies have shed light on vitamin A metabolites; retinaldehyde and retinoic acid and participation of their pathway proteins in the regulation of adipose tissue metabolism and thus, obesity. In this context, we discuss here some of our important findings, which establish the role of vitamin A (supplementation) in obesity and its associated disorders by employing an obese rat model; WNIN/Ob strain. © 2015, Indian Council of Medical Research. All rights reserved. Source


Ray S.,Defence Evaluation and Research Agency | Kulkarni B.,National Institute of Nutrition ICMR | Sreenivas A.,National Institute of Nutrition ICMR
Indian Journal of Medical Research | Year: 2011

Background & objectives: Estimation of prevalence of prehypertension in a population and its association with risk factors of cardiovascular disease is important to design preventive programmes. This cross-sectional study was carried out in a healthy military population to assess the prevalence of prehypertension and its association with risk factors such as overweight, abdominal adiposity and dyslipidaemia. Methods: The study included 767 participants (130 officers and 637 from other ranks). The blood pressure, serum triglycerides and serum cholesterol (total, HDL and LDL) were assessed along with anthropometric measurements such as height, weight, waist-hip ratio in apparently healthy military personnel. Information on smoking, alcohol intake, dietary habits and physical activity was collected using pretested questionnaire. Prehypertension was defined as systolic blood pressure (SBP) 120-139 mm Hg and diastolic blood pressure (DBP) 80-89 mm Hg. Results: The overall prevalence of prehypertension was high (about 80%). The prevalence of other risk factors such as overweight (BMI>23 kg/m2), serum total cholesterol > 200 mg/dl, serum LDL cholesterol > 130 mg/dl, serum HDL cholesterol <40 mg/dl, serum triglyceride > 150 mg/dl in the total group was 30, 22, 22, 67, and 14 per cent, respectively. Most of the personnel undertook moderate or heavy exercise. A significantly higher proportion of individuals with prehypertension had clinical and behavioural risk factors such as overweight, dyslipidaemia and adverse dietary practices like saturated fat and added salt intake. On multivariate logistic regression analysis, prehypertension had significant positive association with BMI>23 kg/m2 (OR 1.75), age (OR 1.89), serum triglyceride >150 mg/dl (OR 2.25)and serum HDL cholesterol <40 mg/dl (OR 1.51). Interpretation & conclusions: The high prevalence of prehypertension and its association with overweight and dyslipidaemia in this young, physically active military population indicates an urgent need for targeted interventions to reduce the cardiovascular risk. Source


Mukhopadhyay S.,DNA Diagnostics Center | Nair S.,DNA Diagnostics Center | Ghosh S.,National Institute of Nutrition ICMR
FEMS Microbiology Reviews | Year: 2012

Tuberculosis (TB) remains a major health problem worldwide. Attempts to control this disease have proved difficult owing to our poor understanding of the pathobiology of Mycobacterium tuberculosis and the emergence of strains that are resistant to multiple drugs currently available for treatment. Genome-wide expression profiling has provided new insight into the transcriptome signatures of the bacterium during infection, notably of macrophages and dendritic cells. These data indicate that M. tuberculosis expresses numerous genes to evade the host immune responses, to suit its intracellular life style, and to respond to various antibiotic drugs. Among the intracellularly induced genes, several have functions in lipid metabolism, cell wall synthesis, iron uptake, oxidative stress resistance, protein secretion, or inhibition of apoptosis. Herein we review these findings and discuss possible ways to exploit the data to understand the complex etiology of TB and to find new effective drug targets. © 2011 Federation of European Microbiological Societies. Source

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