Host-pathogen interactions in tuberculosis patients with type 2 diabetes mellitus

Restrepo, Blanca I.; Schlesinger, Larry S.

doi:10.1016/s1472-9792(13)70004-0

Cited by 89 publications

(85 citation statements)

References 51 publications

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“…Stalenhoef et al (29) detected lower IFN-␥ levels in PBMCs stimulated with MTC from TB patients with or without T2DM. These findings and the current results may appear to be contradictory because T2DM patients are more susceptible to development of active TB; however, these patients also show alterations in the downstream signal transduction of key Th1 and innate immune response cytokines, possibly due to an increase in the levels of advanced glycation end products that can bind and modify protein functions as described by Restrepo et al (15,30). The current work utilized fresh serum, which could explain why differences were not found in the levels of IFN-␥ observed in TB patients with or without T2DM.…”

Section: Discussioncontrasting

confidence: 59%

Clinical Pharmacokinetics of Rifampin in Patients with Tuberculosis and Type 2 Diabetes Mellitus: Association with Biochemical and Immunological Parameters

Medellín‐Garibay

Cortez-Espinosa

Milán-Segovia

et al. 2015

Antimicrob Agents Chemother

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Tuberculosis (TB) remains a major public health issue due to the increasing incidence of type 2 diabetes mellitus (T2DM), which exacerbates the clinical course of TB and increases the risk of poor long-term outcomes. The aim of this study was to characterize the pharmacokinetics of rifampin (RIF) and its relationship with biochemical and immunological parameters in patients with TB and T2DM. The biochemical and immunological parameters were assessed on the same day that the pharmacokinetic evaluation of RIF was performed. Factors related to the metabolic syndrome that is characteristic of T2DM patients were not detected in the TB-T2DM group (where predominant malnutrition was present) or in the TB group. Percentages of CD8؉ T lymphocytes and NK cells were diminished in the TB and TB-T2DM patients, who had high tumor necrosis factor alpha (TNF-␣) and low interleukin-17 (IL-17) levels compared to healthy volunteers. Delayed RIF absorption was observed in the TB and TB-T2DM patients; absorption was poor and slower in the latter group due to poor glycemic control. RIF clearance was also slower in the diabetic patients, thereby prolonging the mean residence time of RIF. There was a significant association between glycemic control, increased TNF-␣ serum concentrations, and RIF pharmacokinetics in the TB-T2DM patients. These altered metabolic and immune conditions may be factors to be considered in anti-TB therapy management when TB and T2DM are concurrently present.

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Section: Discussioncontrasting

confidence: 59%

Clinical Pharmacokinetics of Rifampin in Patients with Tuberculosis and Type 2 Diabetes Mellitus: Association with Biochemical and Immunological Parameters

Medellín‐Garibay

Cortez-Espinosa

Milán-Segovia

et al. 2015

Antimicrob Agents Chemother

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“…It is increasingly clear that although TB and DM have different pathogenic mechanisms, they also share a number of similarities at the molecular level, including key pathways involved in chronic inflammation, metabolism and immunity. [3][4][5] It is critical to gain insight into the factors underlying the links between TB and DM at the molecular, cellular and systemic levels and to integrate data from clinical studies and animal models to better understand the fundamental causes and consequences of the comorbidity.…”

Section: Summary Boxmentioning

confidence: 99%

“…The effect of pre-DM and DM on human immunity to M. tuberculosis during TB and LTBI Recent reviews have addressed the effect of DM on host response to M. tuberculosis 4,6,7 . Studies on human innate immune responses indicate that monocytes from poorlycontrolled DM patients (versus well-controlled or non-DM) have significantly lower binding M A N U S C R I P T…”

Section: Altered Immunitymentioning

confidence: 99%

Defining a Research Agenda to Address the Converging Epidemics of Tuberculosis and Diabetes

Ronacher

Crevel

Critchley

et al. 2017

Chest

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There is growing interest in the re-emerging interaction between type 2 diabetes (DM) and tuberculosis (TB), but the underlying biological mechanisms are poorly understood despite their possible implications in clinical management. Experts in epidemiological, public health, basic science and clinical studies recently convened and identified research priorities for elucidating the underlying mechanisms for the co-ocurrence of TB and DM. We identified gaps in current knowlege of altered immunity in DM patients during TB, where most studies suggest an under-performing innate immunity, but exaggerated adaptive immunity to Mycobacterium tuberculosis. Various molecular mechanisms and pathways that may underly these observations in the DM host. These include signaling induced by excess advanced glycation end products (AGE) and their receptor (RAGE), higher levels of reactive oxidative species and oxidative stress, epigenetic changes due to chronic hyperglycemia, altered nuclear receptors and/or differences in cell metabolism (immuno-metabolism). Studies in humans at different stages of DM (no DM, pre-DM and DM) or TB (latent or active TB) should be complemented with findings in animal models, which provide the unique opportunity to study early events in the host-pathogen interaction. Such studies could also help identify biomarkers that will complement clinical studies in order to tailor the prevention of TB-DM, or avoid the adverse TB treatment outcomes that are more likely in these patients. Such studies will also inform new approaches to host-directed therapies. M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT Summary box• Type 2 diabetes is a syndrome characterised by a range of metabolic (e.g. hyperglycemia, hyperlipidemia), inflammatory, vascular and other changes that may all contribute to increasing TB susceptibility and pathology.• Monocytes and macrophages from diabetic patients and mice have defects leading to altered interactions with M. tuberculosis and delayed adaptive immune responses.• Most human studies have been conducted in patients with active TB, where those with TB-DM comorbidity are characterised by increased secretion of Th1, Th17 and Th2 cytokines. However, the few studies in individuals at risk for TB (LTBI) suggest a different cytokine profile.• Molecular pathways that involve AGE/RAGE, ROS, nuclear receptors and cellular metabolism are potential targets for host-directed therapies to reduce TB susceptibility or pathology in DM patients.• Animal models for TB-DM can improve our understanding of underlying mechanisms and effective treatment approaches for the comorbidity of TB and DM. IntroductionType 2 diabetes mellitus (DM) increases the risk of many infectious diseases, including tuberculosis 1 (TB), and it is now recognized that the increasing DM prevalence in high TB incidence countries such as Sub-Saharan Africa (SSA) is a challenge to TB control. 2 The known association between a chronic syndome like DM and an infectious disease like TB requires the near term development...

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“…DM has also emerged as a common disease of the modern world so it is regarded as a potential risk factor for TB [5][6][7][8][9][10][11]. 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].…”

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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Host-pathogen interactions in tuberculosis patients with type 2 diabetes mellitus

Cited by 89 publications

References 51 publications

Clinical Pharmacokinetics of Rifampin in Patients with Tuberculosis and Type 2 Diabetes Mellitus: Association with Biochemical and Immunological Parameters

Clinical Pharmacokinetics of Rifampin in Patients with Tuberculosis and Type 2 Diabetes Mellitus: Association with Biochemical and Immunological Parameters

Defining a Research Agenda to Address the Converging Epidemics of Tuberculosis and Diabetes

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

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