Expansion of Pathogen-Specific T-Helper 1 and T-Helper 17 Cells in Pulmonary Tuberculosis With Coincident Type 2 Diabetes Mellitus

Kumar, Nathella Pavan; Ramaswamy, Sridhar; Banurekha, Vaithilingam V.; Jawahar, M S; Nutman, Thomas B.; Babu, Subash

doi:10.1093/infdis/jit241

Cited by 100 publications

(120 citation statements)

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“…Indeed, it has been previously demonstrated that CD4 1 T cells producing IL-17A and IFN-g are increased in frequency and magnitude and promote inflammation and that several cytokines produced by Th1 or Th17 cells have been linked to insulin resistance (22)(23)(24). In addition, patients with type 2 diabetes also have been shown to exhibit decreased frequencies of natural regulatory T cells, indicating the presence of an unbalanced proinflammatory milieu in type 2 diabetes (7,24). Thus, underlying poorly controlled diabetes by itself could contribute to the increase in type 1 and 17 cytokines observed in individuals with tuberculosis and diabetes.…”

Section: Discussionmentioning

confidence: 99%

“…Hematology was performed on all individuals, using the Ac$T 5diff hematology analyzer (Beckman Coulter, Brea, CA). This study comprised a separate set of individuals compared with our previous study on tuberculosis and diabetes (7). All individuals were examined as part of a clinical protocol approved by the Institutional Review Board of the National Institute of Research in Tuberculosis (NCT01154959), and informed written consent was obtained from all participants.…”

Section: Study Populationmentioning

confidence: 99%

“…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). In addition, we have previously shown that type 2 diabetes mellitus in tuberculosis disease is associated with elevated frequencies of Th1 and Th17 cells and cytokines (7). Cytokines of the innate and adaptive immune systems orchestrate the immune response to tuberculosis infection, with type 1, type 17, and the IL-1 family of cytokines having been implicated in protection against tuberculosis disease (8) in murine systems whereas type 2 and antiinflammatory cytokines along with type 1 IFNs have been associated with either increased susceptibility to disease and/or enhanced pathology (8).…”

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confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Study Populationmentioning

confidence: 99%

mentioning

confidence: 99%

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

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“…21 Chronic hyperglycemia may disrupt the regulation of key cytokines, such as interferon-gamma, which in turn may increase the M. tuberculosis bacterial burden and subsequent risk of death in TB-DM patients. 22 In addition, altered T-helper (Th) 1, Th 2, and Th 17 cytokine responses have been demonstrated among patients with TB-DM. 23 Diabetes mellitus (DM) is an increasingly recognized comorbidity that can both accelerate TB disease and complicate TB treatment.…”

Section: Discussionmentioning

confidence: 99%

“…22 In addition, altered T-helper (Th) 1, Th 2, and Th 17 cytokine responses have been demonstrated among patients with TB-DM. 23 Diabetes mellitus (DM) is an increasingly recognized comorbidity that can both accelerate TB disease and complicate TB treatment.…”

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confidence: 99%

Outcome and mortality analysis in complicated parapneumonic effusion and empyema

Periasamy

2017

Int J Clin Trials

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Background: Pleural infection is a clinical problem with high mortality and morbidity; 20% of patients with empyema die and approximately 20% require surgery to recover within 12 months of their infection. Studies on pleural infection and their outcome are relevant in developing a scoring system by which failing cases and cases at risk of death can be identified. Methods:The study is retrospective analysis of patient cohort admitted to the tertiary care institute from the period of July 2014 to July 2016 to determine the prognostic factors in the outcome of pleural space infection. The study included all complex, complicated parapneumonic effusion and empyema including tuberculosis above the age of fifteen years. The primary end of the present study was the success or failure. Possible predicting factors for the success or failure of therapy were assessed against this end. Pearson chi square test, χ2 (Fisher's exact test when needed) test was used for discrete data. Logistic regression analysis was applied to adjust for confounding variables to assess the possible predicting factors. Survival plot and analysis using Kaplan Meier method was used. Results: 220 with parapneumonic effusion and empyema were analyzed. Successful outcome was seen in 107 and 113 had failed outcome. Mortality was 30.50%. By logistic regression method the odds of failed outcome were high with diabetes, hypoalbuminemia, loculation, tuberculosis which can predict the outcome especially complicated and complex parapneumonic effusion, empyema (p<0.05). Conclusions: Diabetes, hypoalbuminemia, loculation, tuberculosis should be used in the prediction scoring system. Arivudainambi VP. Int J Clin Trials. 2017 Nov;4(4):176-183 International Journal of Clinical Trials | October-December 2017 | Vol 4 | Issue 4 Page 177 operative intervention. Delay in instituting proper therapy for these effusions is responsible for some of the morbidity associated with parapneumonic effusions. 5 For a simple parapneumonic effusion antibiotics according to culture and sensitivity will suffice. In complicated parapneumonic effusion and empyema intervention in the form of thoracentesis, tube thoracostomy, thoracoscopic intervention, surgery will be needed accordingly. Studies on pleural infection and their outcome are relevant in developing a scoring system by which failing cases and cases at risk of death can be identified.Empyema thoracis (ET) or pyothorax is the inflammatory process of infection in pleural space causing the accumulation and organization of purulent material in the pleural space1; first reported by Hippocrates approximately 2400 years ago.6 According to the American Thoracic Society, the ET process can be divided into three phases: (1) exudative (acute or Stage I), where exudative fluid accumulates without loculation; (2) fibrinopurulent (Stage II), where pleural fluid becomes turbid or purulent with loculation; and (3) organizing (chronic or Stage III), where thickened pus or fibrin peels begin to form, and granulation tissue replacement...

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Diabetes and immunity to tuberculosis

2014

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Summary The dual burden of tuberculosis and diabetes has attracted much attention in the past decade as diabetes prevalence has increased dramatically in countries already afflicted with a high burden of tuberculosis. The confluence of these two major diseases presents a serious threat to global public health; at the same time it also presents an opportunity to learn more about the key elements of human immunity to tuberculosis that may be relevant to the general population. Some effects of diabetes on innate and adaptive immunity which are potentially relevant to tuberculosis defense have been identified, but have yet to be verified in humans and are unlikely to fully explain the interaction of these two disease states. This review provides an update on the clinical and epidemiological features of tuberculosis in the diabetic population and relates them to recent advances in understanding the mechanistic basis of tuberculosis susceptibility and other complications of diabetes. Issues that merit further investigation, such as geographic host and pathogen differences in the diabetes/tuberculosis interaction, the role of hyperglycemia-induced epigenetic reprogramming in immune dysfunction and the impact of diabetes on lung injury and fibrosis caused by tuberculosis, are highlighted in this review.

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Expansion of Pathogen-Specific T-Helper 1 and T-Helper 17 Cells in Pulmonary Tuberculosis With Coincident Type 2 Diabetes Mellitus

Cited by 100 publications

References 33 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

Outcome and mortality analysis in complicated parapneumonic effusion and empyema

Diabetes and immunity to tuberculosis

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