Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Eur J Clin Microbiol Infect Dis ; 37(2): 371-380, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29189980

ABSTRACT

Patients with diabetes mellitus have an increased risk of developing tuberculosis. Although the underlying mechanism is unclear, evidence suggests a role for chronic hyperglycaemia. We examined the influence of hyperglycaemia on Mycobacterium tuberculosis-induced cytokine responses in patients with type 1 diabetes mellitus (T1D). Peripheral blood mononuclear cells (PBMCs) from 24 male T1D patients with sub-optimal glucose control [HbA1c > 7.0% (53 mmol/L)] and from 24 age-matched male healthy controls were stimulated with M. tuberculosis lysate. Cytokine analysis, assessment of aerobic glycolysis, receptor recognition and serum cross-over experiments were performed to explore the mechanistic differences. PBMCs from T1D patients produced less bioactive interleukin (IL)-1ß in response to M. tuberculosis. IL-6 and interferon (IFN)-γ production trended towards a decrease, whilst other cytokines such as tumour necrosis factor (TNF)-α, IL-17 and IL-1Ra were normal. The decrease in cytokine production was not correlated to HbA1c or plasma glucose levels. Cross-over serum experiments did not alter the cytokine profile of T1D or control patients, arguing for an intrinsic cellular defect. Cellular metabolism and the expression of M. tuberculosis-related pattern recognition receptors (PRRs) such as TLR2, TLR4 and NOD2 did not differ between T1D patients and healthy controls. Compared to matched controls, T1D patients have a reduced capacity to produce pro-inflammatory cytokines in response to M. tuberculosis. The impaired IL-1ß production in T1D patients may contribute to the increased susceptibility to tuberculosis. This effect appears not to be related to prevailing glucose levels but to an intrinsic cellular deficit.


Subject(s)
Diabetes Mellitus, Type 1/immunology , Disease Susceptibility/immunology , Interleukin-1beta/biosynthesis , Leukocytes, Mononuclear/immunology , Mycobacterium tuberculosis/immunology , Tuberculosis, Pulmonary/epidemiology , Blood Glucose , Glucose/metabolism , Glycated Hemoglobin/analysis , Humans , Hyperglycemia/immunology , Interferon-gamma/biosynthesis , Interleukin 1 Receptor Antagonist Protein/biosynthesis , Interleukin-17/biosynthesis , Interleukin-6/biosynthesis , Male , Middle Aged , Tuberculosis, Pulmonary/microbiology , Tumor Necrosis Factor-alpha/biosynthesis
2.
Clin Exp Allergy ; 46(12): 1564-1574, 2016 12.
Article in English | MEDLINE | ID: mdl-27474157

ABSTRACT

BACKGROUND: STAT1 mutations cause chronic mucocutaneous candidiasis (CMC), while STAT3 mutations cause hyper-IgE syndrome (HIES). CMC and HIES patients have T helper (Th) 17 defects suffering from mucosal Candida infections, but only patients with HIES show an allergic phenotype with eczema, eosinophilia and high IgE levels. OBJECTIVE: We investigated whether differential Th2 and Th9 responses may explain the clinical differences. METHODS: Peripheral blood mononuclear cells of patients with CMC (n = 4), patients with HIES (n = 4), patients with atopic dermatitis (n = 4) and healthy volunteers (n = 13) were stimulated with Candida and Staphylococcus aureus, with and without IL-4. The cytokines IL-5, IL-13, IL-9, IL-17 and TGFß and regulatory T cells were measured in cell culture supernatants by ELISA or flow cytometry, respectively. RESULTS: Peripheral blood mononuclear cells of patients with CMC showed a significantly impaired production of the Th2 cytokines IL-5 and IL-13, especially in the presence of IL-4. Moreover, IL-9 production was significantly lower in patients with CMC compared to healthy controls. In contrast, patients with HIES and patients with AD showed normal IL-5 and IL-13 production, while IL-9 production was significantly lower in patients with HIES compared to healthy controls. Although TGFß was involved in the IL-4-induced IL-9 production, TGFß levels and the frequency of regulatory T cells did not differ between patients with HIES and controls. Flow cytometry analysis demonstrated an IL-9+ IL-17+ CD4+ subset in healthy controls after stimulation with Candida which was less present in patients with HIES. CONCLUSION: Patients with CMC have a general Th defect including Th2 and Th9, while patients with HIES have normal Th2 cytokines. These differences are in line with their clinical presentation. Surprisingly, the allergic cytokine IL-9 was deficient in both HIES and CMC, suggesting a Th-17-derived origin.


Subject(s)
Candidiasis, Chronic Mucocutaneous/diagnosis , Candidiasis, Chronic Mucocutaneous/immunology , Job Syndrome/diagnosis , Job Syndrome/immunology , T-Lymphocytes, Helper-Inducer/immunology , Adult , Aged , Biomarkers , Candidiasis, Chronic Mucocutaneous/metabolism , Candidiasis, Chronic Mucocutaneous/therapy , Case-Control Studies , Cytokines/blood , Cytokines/metabolism , Eosinophils/immunology , Eosinophils/metabolism , Female , Humans , Immunoglobulin E/blood , Immunoglobulin E/immunology , Job Syndrome/metabolism , Job Syndrome/therapy , Leukocyte Count , Male , Middle Aged , Phenotype , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , T-Lymphocytes, Helper-Inducer/metabolism , Th2 Cells/immunology , Th2 Cells/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...