Patients with type 1 diabetes mellitus have impaired IL-1β production in response to Mycobacterium tuberculosis

Autor: Mihai G. Netea, J.A. van Diepen, C.J.J. Tack, B.E. de Galan, Anneke Hijmans, R. van Crevel, Ekta Lachmandas, C.N.A.M. van den Heuvel, Kathrin Thiem
Rok vydání: 2017
Předmět:
Blood Glucose
Male
0301 basic medicine
endocrine system diseases
medicine.medical_treatment
Interleukin-1beta
lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4]
0302 clinical medicine
030212 general & internal medicine
GeneralLiterature_REFERENCE(e.g.
dictionaries
encyclopedias
glossaries)
biology
Interleukin-17
Interleukin
Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6]
General Medicine
Middle Aged
3. Good health
Infectious Diseases
Cytokine
Original Article
Disease Susceptibility
Microbiology (medical)
Tuberculosis
Peripheral blood mononuclear cell
Mycobacterium tuberculosis
Interferon-gamma
03 medical and health sciences
All institutes and research themes of the Radboud University Medical Center
Diabetes mellitus
medicine
Humans
Tuberculosis
Pulmonary
Glycated Hemoglobin
Type 1 diabetes
Interleukin-6
Tumor Necrosis Factor-alpha
business.industry
nutritional and metabolic diseases
medicine.disease
biology.organism_classification
Interleukin 1 Receptor Antagonist Protein
lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4]
Diabetes Mellitus
Type 1
Glucose
030104 developmental biology
Anaerobic glycolysis
Hyperglycemia
Immunology
Leukocytes
Mononuclear
business
Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19]
Zdroj: European Journal of Clinical Microbiology & Infectious Diseases
European Journal of Clinical Microbiology and Infectious Diseases, 37, 371-380
European Journal of Clinical Microbiology and Infectious Diseases, 37, 2, pp. 371-380
ISSN: 1435-4373
0934-9723
DOI: 10.1007/s10096-017-3145-y
Popis: 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)-1β 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-1β 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. Electronic supplementary material The online version of this article (10.1007/s10096-017-3145-y) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
Externí odkaz: