title: Impaired toll-like receptor signalling in peripheral B cells from newly diagnosed type-2 diabetic subjects.
abstract: Toll-like receptors (TLRs) under diabetic conditions trigger inflammation and impair immunity. In the present study, we looked at the expression of TLRs (2 and 4) and their adaptors in Normal Glucose Tolerant (NGT), Newly Diagnosed Type-2 Diabetic (NDD) and Known Type-2 Diabetic (KDM) subjects. We also estimated TLR induced cytokine secretion, cellular activation and apoptosis. Surface expression of TLR2 and 4 was significantly reduced in the B cells of the NDD subjects and was associated with decreased cellular activation and cytokine secretion (TNF-α and IL-6). This impairment was not due to B cell deficiency or apoptosis or immunosuppressive cytokine (IL-10 and TGF-β) secretion. However, the upregulation of immunomodulatory enzymes (Arg-1, HO-1 and IDO) could probably account for the reduced TLR expression. The defective TLR signalling was largely ameliorated in the KDM group which might be due to the use the anti-diabetic drugs which have anti-inflammatory effect.
authors.affiliation: AU-KBC Research Centre, MIT Campus of Anna University, Chennai 600 044, India.
authors.forename: Haridoss
authors.initials: H
authors.lastname: Madhumitha
authors.affiliation: Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialties Centre, WHO Collaborating Centre for Non-Communicable Diseases Prevention and Control, International Diabetes Federation (IDF) Centre for Education, Chennai, India.
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Mohan
authors.affiliation: National Institutes of Health-International Centre for Excellence in Research, National Institute for Research in Tuberculosis, Chennai, India.
authors.forename: Nathella P
authors.initials: NP
authors.lastname: Kumar
authors.affiliation: Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialties Centre, WHO Collaborating Centre for Non-Communicable Diseases Prevention and Control, International Diabetes Federation (IDF) Centre for Education, Chennai, India.
authors.forename: Rajendra
authors.initials: R
authors.lastname: Pradeepa
authors.affiliation: National Institutes of Health-International Centre for Excellence in Research, National Institute for Research in Tuberculosis, Chennai, India.
authors.forename: Subash
authors.initials: S
authors.lastname: Babu
authors.affiliation: AU-KBC Research Centre, MIT Campus of Anna University, Chennai 600 044, India; Dept of Genetics, Dr ALM PG IBMS, University of Madras, Taramani, Chennai, India. Electronic address: cvaravindhan@gmail.com.
authors.forename: Vivekanandhan
authors.initials: V
authors.lastname: Aravindhan
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000175:diagnosis / Q000276:immunology*; D005260:Female; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D037181:Lectins, C-Type / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D016753:Interleukin-10; D015850:Interleukin-6; D037181:Lectins, C-Type; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D000099192:CD69 Antigens; C576710:IDO1 protein, human; C508609:IL10 protein, human; C439524:TNF protein, human
keywords: CD69; IL-6; TLR2; TLR4; TNF-α