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

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)-1? in response to M. tuberculosis. IL-6 and interferon (IFN)-? production trended towards a decrease, whilst other cytokines such as tumour necrosis factor (TNF)-?, 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-1? 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.

SUBMITTER: Lachmandas E

PROVIDER: S-EPMC5780542 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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

Lachmandas E E Thiem K K van den Heuvel C C Hijmans A A de Galan B E BE Tack C J CJ Netea M G MG van Crevel R R van Diepen J A JA

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology 20171130 2

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 co ...[more]

PMID: 29189980

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Project description:BackgroundA paucity of studies focused on the genetic association that tuberculosis (TB) patients with non-communicable diseases (NCDs) are more likely to be infected with Mycobacterium tuberculosis (MTB) with more potent virulence on anti-TB drug resistance than those without NCDs. The study aimed to document the predominant genotype, determine the association between MTB genotypes and NCD status and drug resistance.MethodsWe conducted a molecular study in 105 TB patients based on a cross-sectional study focused on the comorbid relationship between chronic conditions and TB among 1773 subjects from September 1, 2019 to August 30, 2020 in Guizhou, China. The participants were investigated through face-to-face interviews, followed by NCDs screening. The DNA of MTB isolates was extracted prior to genotyping using 24 loci MIRU-VNTR. The subsequent evaluations were performed by phylogenetic trees, combined with tests of statistical power, Chi-square or Fisher and multivariate logistic regression analysis.ResultsThe Beijing family of Lineage 2 (East Asia) was the predominant genotype accounting for 43.8% (46/105), followed by Lineage 4 (Euro-America) strains, including Uganda I (34.3%, 36/105), and the NEW-1 (9.5%, 10/105). The proportion of Beijing strain in patients with and without NCDS was 28.6% (8/28) and 49.4% (38/77), respectively, with a statistical power test value of 24.3%. No significant association was detected between MTB genotype and NCD status. A low clustering rate (2.9%) was identified, consisting of two clusters. The rates of global, mono-, poly- and multi-drug resistance were 16.2% (17/105), 14.3% (15/105), 1.0% (1/105) and 4.8% (5/105), respectively. The drug-resistant rates of rifampicin, isoniazid, and streptomycin, were 6.7% (7/105), 11.4% (12/105) and 5.7% (6/105), respectively. Isoniazid resistance was significantly associated with the Beijing genotype of Lineage 2 (19.6% versus 5.1%).ConclusionsThe Lineage 2 East Asia/Beijing genotype is the dominant genotype of the local MTB with endogenous infection preponderating. Not enough evidence is detected to support the association between the MTB genotype and diabetes/hypertension. Isoniazid resistance is associated with the Lineage 2 East Asia/Beijing strain.

Dataset Information

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

Publications

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

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