lipoteichoic-acid and Diabetes-Mellitus--Type-1

Metabolic alterations associated with diabetes mellitus alter innate immunity. Dogs often develop infectious or inflammatory complications related to diabetes mellitus, yet little is known about the effects of diabetes mellitus on the immune system in this species.. Prospective evaluation in dogs with poorly regulated spontaneous type 1 diabetes mellitus (T1DM). In vitro leukocyte cytokine response to lipopolysaccharide (LPS), lipoteichoic acid (LTA), and peptidoglycan (PG) was compared between dogs with T1DM and healthy dogs. Additionally, the effect of acute in vitro glucose exposure on leukocyte tumor necrosis factor (TNF) production from healthy dogs was measured.. Leukocytes from dogs with T1DM had significantly greater TNF production after LTA and PG stimulation compared with leukocytes from healthy dogs. Leukocyte interleukin (IL)-6 production was greater after stimulation with LPS, LTA, PG, and phosphate-buffered saline in the T1DM group. No such difference was noted when evaluating IL-10 production between groups regardless of stimulant. Dogs with T1DM had significantly greater IL-6 to IL-10 production ratios than healthy dogs. Acute exposure to dextrose did not augment cytokine production from healthy canine leukocytes.. Dogs with T1DM have altered innate immunity characterized by upregulation of proinflammatory cytokine production without a concurrent change in anti-inflammatory cytokine production. This may be one explanation for the common infectious and inflammatory complications associated with T1DM in dogs.

Topics: Animals; Bacterial Infections; Blood Glucose; Case-Control Studies; Cytokines; Diabetes Mellitus, Type 1; Dog Diseases; Dogs; Female; Hypoglycemic Agents; Immunity, Innate; Inflammation; Inflammation Mediators; Insulin; Interleukin-10; Interleukin-6; Leukocytes; Lipopolysaccharides; Male; Peptidoglycan; Teichoic Acids; Tumor Necrosis Factor-alpha; Up-Regulation

To investigate the differences of Toll-like receptors (TLRs) expression and response of monocyte and modulation of 1,25-dihydroxy-vitamin D3 on monocyte activity. Peripheral blood monocytes were collected from 23 healthy controls, 18 latent autoimmune diabetes in adults (LADA), and 22 type 2 diabetes mellitus (T2DM), respectively. CD14, TLR2 and TLR4 expression were analyzed. Moreover, the effect of 1,25-dihydroxy-vitamin D3 (1,25(OH)(2)D3) on monocyte response to lipoteichoic acid (LTA) and lipopolysaccharide (LPS) was evaluated in vitro by measuring phosphorylation level of NF-kappaB-p65 and associated cytokine production. Monocytes showed significantly higher surface CD14 expression from LADA compared with that from T2DM and controls, and high expression of TLR4 from LADA and T2DM than controls. After incubation with LPS or LTA, decreased surface expressions of CD14 were observed on monocytes from T2DM and controls, in contrast to the increased on monocytes from LADA. Activation of NF-kappaB and amounts of IL-1beta and TNF-alpha production by stimulation with ligands significantly increased in LADA and T2DM, which was modulated by 1,25(OH)(2)D3 to similar level, as compared to controls. The modulation of 1,25(OH)(2)D3 on monocytes makes us to consider more potency of vitamin D3 as therapy in LADA and T2DM.

Topics: Adult; Calcitriol; Cells, Cultured; Cytotoxicity, Immunologic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Evaluation, Preclinical; Female; Humans; Ligands; Lipopolysaccharide Receptors; Lipopolysaccharides; Male; Middle Aged; Monocytes; Teichoic Acids; Toll-Like Receptor 2; Toll-Like Receptor 4; Toll-Like Receptors

Altered Toll-like receptors (TLRs) expression and response of monocyte may be associated with insulin sensitivity, obesity and diabetes.. Peripheral blood monocytes were respectively collected from 23 healthy controls, 16 type 1 diabetes mellitus (T1DM), and 18 latent autoimmune diabetes in adults (LADA). CD14, TLR2 and TLR4 expression were analyzed by flow cytometer. Moreover, the effect of 1, 25-dihydroxy-vitamin D3 (1,25(OH)(2)D3) on monocyte response to lipoteichoic acid (LTA) and lipopolysaccharide (LPS) was evaluated in vitro by measuring phosphorylation concentration of NF-kappaB-p65 and associated cytokine production.. Monocytes showed significantly higher surface CD14 and TLR4 expressions from LADA and lower CD14 expression from T1DM than controls. TLRs ligands decreased monocyte CD14 expression in T1DM but increased in LADA. Monocyte hyperresponsiveness to ligands was modulated by 1,25(OH)(2)D3 to similar concentration, as compared to controls.. Monocytes from T1DM and LADA showed similar cellular reactivity towards ligands and 1,25(OH)2D3 was observed to restore this defect to a certain extent in vitro.

Topics: Adult; Diabetes Mellitus, Type 1; Female; Humans; Interleukin-1beta; Lipopolysaccharide Receptors; Lipopolysaccharides; Male; Middle Aged; Monocytes; NF-kappa B; Teichoic Acids; Toll-Like Receptor 2; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha; Vitamin D

IgG antibody levels to lipoteichoic acid (LTA), prepared from Streptococcus mutans cells, were determined by enzyme-linked immunosorbent assay in serum samples from 149 subjects. An extract from Bacteroides gingivalis and lipopolysaccharide from Escherichia coli 055:B5 served as control antigens. The reference group comprised 28 systemically and periodontally healthy adults. The main test groups were: 52 persons with gingivitis only, and 69 patients with periodontitis. Within those groups, 37 patients had insulin-dependent diabetes mellitus, another 20 patients were prospective or renal transplant recipients. The periodontitis patient group showed significantly (p less than 0.05) higher mean antibody value and higher frequency of extreme antibody responses to both LTA and B. gingivalis than the gingivitis group. LPS did not discriminate between the groups. Multiple regression analysis with gingivitis scores as the dependent variable selected plaque scores, anti-LTA antibody values and general health status as significant (p less than 0.05) regressors. The variance in radiographical alveolar bone loss was significantly (p less than 0.05) explained by age and by antibody values to B. gingivalis and to LTA. The patients with extreme immunological responsiveness to LTA or to B. gingivalis had about twice as much alveolar bone loss as those with normal serological reactivity. The results support the contention that LTA modulates the progression of periodontitis in humans.

Topics: Adolescent; Adult; Antigen-Antibody Reactions; Bone Resorption; Diabetes Mellitus, Type 1; Enzyme-Linked Immunosorbent Assay; Gingivitis; Humans; Immunoglobulin G; Immunosuppression Therapy; Kidney Failure, Chronic; Lipopolysaccharides; Middle Aged; Periodontitis; Teichoic Acids