Mycobacterial antigen-induced T helper type 1 (Th1) and Th2 reactivity of peripheral blood mononuclear cells from diabetic and non-diabetic tuberculosis patients and<i>Mycobacterium bovis</i>bacilli Calmette–Guérin (BCG)-vaccinated healthy subjects

Al‐Attiyah, Rajaa; Mustafa, Abu Salim

doi:10.1111/j.1365-2249.2009.04000.x

Cited by 66 publications

(66 citation statements)

References 51 publications

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“…Several early studies reported reduced proinflammatory cytokines in patients with diabetes after infection with Mycobacterium tuberculosis (3,4). Two studies, however, reported the elevation of helper T-cell type 1 (Th1) cytokines in tuberculosis-infected diabetic hosts; one was conducted in streptozocin-treated mice (5) and another in diabetic and nondiabetic patients with tuberculosis (6).…”

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confidence: 99%

Type 2 Diabetes Mellitus Coincident with Pulmonary Tuberculosis Is Associated with Heightened Systemic Type 1, Type 17, and Other Proinflammatory Cytokines

et al. 2013

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Rationale: Type 2 diabetes mellitus is a major risk factor for the development of active tuberculosis, although the biological basis underlying this susceptibility remains poorly characterized. Objectives and Methods:To identify the influence of coincident diabetes mellitus on cytokine levels in pulmonary tuberculosis, we examined circulating levels of a panel of cytokines and chemokines in the plasma of individuals with tuberculosis with diabetes and compared them with those of individuals without diabetes. Measurements and Main Results:Tuberculosis with diabetes is characterized by elevated circulating levels of type 1 (IFN-g, tumor necrosis factor-a, and IL-2), type 2 (IL-5), and type 17 (IL-17A) cytokines but decreased circulating levels of IL-22. This was associated with increased systemic levels of other proinflammatory cytokines (IL-1b, IL-6, and IL-18) and an antiinflammatory cytokine (IL-10) but not type 1 IFNs. Moreover, tuberculosis antigenstimulated whole blood also showed increased levels of proinflammatory cytokines. Finally, type 1 and type 17 cytokines in plasma exhibit a significant positive correlation with hemoglobin A1C levels, indicating that impaired control of diabetes is associated with this proinflammatory milieu. Multivariate analysis revealed that the association of proinflammatory cytokines with diabetes mellitus was not influenced by age, sex, or other metabolic parameters.Conclusions: Our data reveal that tuberculosis with diabetes is characterized by heightened cytokine responsiveness, indicating that chronic inflammation underlying type 2 diabetes potentially contributes to increased immune pathology and poor control in tuberculosis infection.

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confidence: 99%

Type 2 Diabetes Mellitus Coincident with Pulmonary Tuberculosis Is Associated with Heightened Systemic Type 1, Type 17, and Other Proinflammatory Cytokines

et al. 2013

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“…Increased Th2 responses have been postulated to play a role in susceptibility to TB, as IL-4 and IL-13 can undermine Th1-mediated immunity and drive inappropriate alternative activation of macrophages [40,41]. Previous studies suggest that TB patients have higher Th2 cells [42] and diabetic TB patients susceptible to TB partially come from a higher Th2 bias [43]. The ratios of Th1 cells to Th2 cells were higher and the proportion of Th2 cells and ratios of Th2 cells to Th17 cells were lower in peripheral blood from PTB patients, suggesting that the dynamic balance of Th1, Th2 and Th17 cells may influence the outcome of M. tuberculosis infection.…”

Section: Discussionmentioning

confidence: 99%

IFN-<i>γ</i>-, IL-4-, IL-17-, PD-1-Expressing T Cells and B Cells in Peripheral Blood from Tuberculosis Patients

He¹,

Huang²,

Li³

et al. 2012

AiM

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Although the efficacy of tuberculosis (TB) vaccines is tightly linked to cell-mediated immunity, some functions of T and B cells in TB patients remain unclear. To address how Mycobacterium tuberculosis infection inhibits T effector responses, we assessed the proportions of T cell subsets and B cells in peripheral blood from pulmonary TB (PTB) patients, pleural TB (PLTB) patients, and healthy subjects (HS, who showed purified protein derivative (PPD)-positive reactions) with flow cytometry. Compared to HS, PTB and PLTB patients exhibited higher proportions of B cells and Th17 cells, and lower proportions of Th2 cells and ratios of Th1 to Th17 cells and of Th2 to Th17 cells. PTB patients had higher CD4 + T cells and PD-1 + CD4 + T cells than HS. Newly diagnosed PTB patients (nPTB) had higher proportions of B cells than HS; in contrast, PTB patients subjected to effective treatments (oPTB) and HS shared similar proportions of B cells. oPTB patients had higher proportions of CD4 + T cells, Th17 cells, and PD-1 + CD4 + T cells than HS, but this difference did not occur in nPTB patients. These findings suggest that shifting ratios of Th1 to Th17 cells may be beneficial for M. tuberculosis to amplify.

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“…It is believed that diabetic patients have compromised immunity, which makes them more susceptible to bacterial infections such as tuberculosis [12,13]. But still the molecular link between tuberculosis and diabetes is not clearly understood [14]. Our investigation was aimed to understand the molecular link between DM and TB.…”

Section: Introductionmentioning

confidence: 99%

VDR, RXR, Coronin-1 and Interferonγ Levels in PBMCs of Type-2 Diabetes Patients: Molecular Link between Diabetes and Tuberculosis

2014

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Diabetes and tuberculosis are world's most deadly epidemics. People suffering from diabetes are susceptible to tuberculosis. Molecular link between the two is largely unknown. It is known that Vitamin A receptor (RXR) heterodimerizes with Vitamin D receptor (VDR) and Peroxisome proliferator-activator receptor-c (PPARc) to regulate Tryptophan-aspartate containing coat protein (TACO) expression and fatty acid metabolism respectively, so it would be interesting to check the expression of these genes in diabetes mellitus (DM) patients which might explain the susceptibility of diabetics to tuberculosis. In this study, we checked the expression of RXR, VDR, TACO and Interferon-c (IFNc) genes in type-2 DM patients for understanding the link between the two diseases. We observed down regulation of RXR gene and corresponding up regulation of TACO gene expression. We have not observed significant change in expression of VDR and IFNc genes in type-2 DM patients. Repression of RXR gene could hamper VDR-RXR heterodimer formation and thus would up regulate TACO gene expression which may predispose the type-2 DM patients to tuberculosis. Also, decrease in RXR-PPARc heterodimer could be involved in DM.

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Mycobacterial antigen-induced T helper type 1 (Th1) and Th2 reactivity of peripheral blood mononuclear cells from diabetic and non-diabetic tuberculosis patients andMycobacterium bovisbacilli Calmette–Guérin (BCG)-vaccinated healthy subjects

Cited by 66 publications

References 51 publications

Type 2 Diabetes Mellitus Coincident with Pulmonary Tuberculosis Is Associated with Heightened Systemic Type 1, Type 17, and Other Proinflammatory Cytokines

Type 2 Diabetes Mellitus Coincident with Pulmonary Tuberculosis Is Associated with Heightened Systemic Type 1, Type 17, and Other Proinflammatory Cytokines

IFN-<i>γ</i>-, IL-4-, IL-17-, PD-1-Expressing T Cells and B Cells in Peripheral Blood from Tuberculosis Patients

VDR, RXR, Coronin-1 and Interferonγ Levels in PBMCs of Type-2 Diabetes Patients: Molecular Link between Diabetes and Tuberculosis

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Mycobacterial antigen-induced T helper type 1 (Th1) and Th2 reactivity of peripheral blood mononuclear cells from diabetic and non-diabetic tuberculosis patients andMycobacterium bovisbacilli Calmette–Guérin (BCG)-vaccinated healthy subjects

Cited by 66 publications

References 51 publications

Type 2 Diabetes Mellitus Coincident with Pulmonary Tuberculosis Is Associated with Heightened Systemic Type 1, Type 17, and Other Proinflammatory Cytokines

Type 2 Diabetes Mellitus Coincident with Pulmonary Tuberculosis Is Associated with Heightened Systemic Type 1, Type 17, and Other Proinflammatory Cytokines

IFN-&lt;i&gt;γ&lt;/i&gt;-, IL-4-, IL-17-, PD-1-Expressing T Cells and B Cells in Peripheral Blood from Tuberculosis Patients

VDR, RXR, Coronin-1 and Interferonγ Levels in PBMCs of Type-2 Diabetes Patients: Molecular Link between Diabetes and Tuberculosis

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IFN-<i>γ</i>-, IL-4-, IL-17-, PD-1-Expressing T Cells and B Cells in Peripheral Blood from Tuberculosis Patients