Diabetes and immunity to tuberculosis

Abstract

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.

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

“…In contrast, CD8 ϩ T cells are generally thought to contribute to optimal immunity and protection, and a recent study demonstrated that these cells could be a better biomarker of the protective response to TB and the response to therapy than CD4 ϩ T cells (25,26). The relevance of innate cells such as monocytes/macrophages and NK cells has been well described (8). However, no studies on T-cell subpopulations, monocytes, and NK cell status have been performed in the context of RIF pharmacokinetics in TB-T2DM patients to date.…”

“…A standard low-fat diet was provided 3, 6, and 12 h after medication intake; the patients were allowed to ingest water ad libitum (17,18). After the drugs were administered, blood samples were collected 0.33, 0.66, 1, 1.5, 2, 2.5, 3,4,6,8,12, and 24 h postdose. Plasma was immediately separated and frozen at Ϫ80°C prior to analysis.…”

“…CD4 ϩ T lymphocytes in combination with cytokines such as gamma interferon (IFN-␥) and tumor necrosis factor alpha (TNF-␣) are fundamental for control of the infection (7). However, active TB in patients with T2DM is characterized by an increased but delayed adaptive response involving CD4 ϩ T cells and cytokines (8). Other types of cells, such as CD8 ϩ T lymphocytes, monocytes, and natural killer (NK) cells, are also involved in anti-MTC immunity, but their role in T2DM susceptibility to TB infection is unclear (7,8).…”

“…However, active TB in patients with T2DM is characterized by an increased but delayed adaptive response involving CD4 ϩ T cells and cytokines (8). Other types of cells, such as CD8 ϩ T lymphocytes, monocytes, and natural killer (NK) cells, are also involved in anti-MTC immunity, but their role in T2DM susceptibility to TB infection is unclear (7,8). Biochemical and immunological parameters reflect the pathophysiological status of TB patients with or without T2DM, and the pharmacokinetics (PK) of a drug may be modified according to a patient's condition.…”

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

“…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].…”