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1.
Cytokine ; 156: 155918, 2022 08.
Article in English | MEDLINE | ID: mdl-35640417

ABSTRACT

Pan-leukocyte exhaustion is a physiological process associated with immune homeostasis. Too much of immune exhaustion can lead to immune impairment and increased susceptibility to infections and cancer; too little can lead to chronic inflammation. Since type-2 diabetes subjects have both impaired immunity and metainflammation, we looked at TLR induced pan-immune exhaustion and its regulation, in these subjects. TLR induced expression of PD-1 and CTLA-4 in T cells, B cells, monocytes and neutrophils, in whole blood cultures, were quantified by flowcytometry. Circulating levels and in vitro secretion of IFN-ß and α-Defensin-1 (α-DEF-1) were quantified by ELISA. TLR induced expression of PU.1, IRF-3,-4 and -5 in whole blood cultures was quantified by qRT-PCR. Systemic lipid and protein peroxidation was quantified by spectrophotometry. TLR induced expression of PD-1 (in monocytes) and CTLA-4 expression (in B cells and neutrophils) were decreased in drug naive newly diagnosed diabetes patients. This was associated with decreased secretion and circulating levels of IFN-ß and increased secretion and circulating levels of α-DEF-1 in these subjects. No major derangement in the transcriptional network was seen. Many of these defects were only partially rectified in those under treatment. Together, we hypothesize that the high defensin levels could inhibit TLR signalling leading to reduced IFN-ß levels, which in turn could lead to reduced expression of PD-1 and CTLA-4 in the immune cells. This effect along with systemic redox stress could fuel metainflammation in type-2 diabetes.


Subject(s)
Diabetes Mellitus, Type 2 , alpha-Defensins , CTLA-4 Antigen/metabolism , Diabetes Mellitus, Type 2/metabolism , Humans , Interferon-beta/metabolism , Monocytes/metabolism , Programmed Cell Death 1 Receptor , alpha-Defensins/metabolism
2.
Front Endocrinol (Lausanne) ; 13: 1011942, 2022.
Article in English | MEDLINE | ID: mdl-36482987

ABSTRACT

Aim: Metabolic syndrome (MS) refers to a group of co-morbidities which include central obesity, hypertension, hyperglycemia and dyslipidemia. Previously, we reported that childhood lymphatic filariasis (LF) confers significant protection against type-1 and type-2 forms of diabetes, by means of immunomodulation. In the present study, we studied the effect of LF on endocrine dysfunction in MS and Non-MS patients in baseline and after 10 years of follow-up. Methods: We quantified the serum levels of pancreatic hormones (insulin and glucagon), incretins (Ghrelin, GIP and GLP-1) and adipokines (leptin, adiponectin, adipsin, visfatin, PAI-1 and resistin) by multiplex bead array system. Results: MS (both LF- and LF+) subjects had increased insulin levels compared to NMS (both LF- and LF+) subjects. MS-LF+ subjects had significantly increased levels of glucagon, ghrelin, GIP and GLP-1 and decreased levels of adipsin, compared to MS-LF- subjects. Interestingly this effect was short-lived and was not seen in the follow-up samples. Conclusion: Overall, LF infection might confer limited short-term beneficial effects against MS, by means of modulating the incretin levels,either directly or indirectly.


Subject(s)
Metabolic Syndrome , Humans , Child , Glucagon , Insulin
3.
Front Immunol ; 12: 716515, 2021.
Article in English | MEDLINE | ID: mdl-34566972

ABSTRACT

Metainflammation, as seen in chronic diabetes subjects, impairs immunity and increases the susceptibility to infections. In the present study, the effect of diabetes on immune response against filariasis was studied. Both toll-like receptor (TLR)-mediated and crude antigen-induced immune responses were quantified, in whole blood cultures from filariasis-infected subjects (LF+), with and without diabetes. Blood cultures were stimulated with TLR ligands (TLR2 and TLR4) or filarial antigen or were left unstimulated (control) for 18 h. Cytokine, chemokine, and defensin secretion was quantified by ELISA. Expression of HLA-DR, B7-1, B7-2, activation marker (CD69), and Th (Th1, Th2, Th17, and Th9) phenotypes was quantified by flow cytometry. Expression of immunomodulatory effectors (Cox-2, HO-1, IDO-1, and p47Phox) and Th-polarizing transcription factors (T-bet, GATA3, and ROR-γt) was quantified by quantitative PCR. Secretion of IL-27, IL-1Ra, IL-12, IL-33, IL-9, and SDF-1 was increased under diabetes conditions with increased Th9 polarization and increased expression of Cox-2 and IDO. Overall, diabetes was found to augment both TLR-mediated and antigen-induced inflammation, which can promote chronic pathology in LF+ subjects.


Subject(s)
Adaptive Immunity , Diabetes Complications , Disease Susceptibility , Filariasis/etiology , Immunity, Innate , Antigens/metabolism , Biomarkers , Comorbidity , Cytokines/metabolism , Diabetes Mellitus, Type 2/complications , HLA Antigens/immunology , Humans , Immunomodulation , Inflammation Mediators/metabolism , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , Toll-Like Receptors/metabolism
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