Influence of diabetes mellitus on immunity to human tuberculosis

Abstract

Type 2 diabetes mellitus(DM) is a major risk factor for the development of active pulmonary tuberculosis (TB), with development of DM pandemic in countries where TB is also endemic. Understanding the impact of DM on TB and the determinants of co-morbidity is essential in responding to this growing public health problem with improved therapeutic approaches. Despite the clinical and public health significance posed by the dual burden of TB and DM, little is known about the immunological and biochemical mechanisms of susceptibility. One possible mechanism is that an impaired immune response in patients with DM facilitates either primary infection with Mycobacterium tuberculosis or reactivation of latent TB. Diabetes is associated with immune dysfunction and alterations in the components of the immune system, including altered levels of specific cytokines and chemokines. Some effects of DM on adaptive immunity that are potentially relevant to TB defence have been identified in humans. In this review, we summarize current findings regarding the alterations in the innate and adaptive immune responses and immunological mechanisms of susceptibility of patients with DM to M. tuberculosis infection and disease.

Keywords: B cells; T cells; diabetes mellitus; latent tuberculosis; monocytes and dendritic cells; tuberculosis.

Figure 1

Influence of diabetes mellitus (DM) on latent and active tuberculosis (TB). The CD4⁺ T‐cell responses to mycobacterial antigens in individuals with latent TB with or without DM is summarized in terms of T helper type 1 (Th1), Th2 and Th17 profiles (a). The CD4⁺ T‐cell responses to mycobacterial antigens in individuals with active TB with or without DM is summarized in terms of Th1, Th17 and regulatory T (Treg) cell profiles (b).

Figure 2

Alterations in the frequencies of CD4⁺ T‐cell, CD8⁺ T‐cell, B‐cell, monocyte and dendritic cell subsets in tuberculosis‐diabetes (TB‐DM) co‐morbidity. Frequency distribution of CD4⁺ naive, central memory (CM) or effector memory (EM) subsets in active pulmonary TB with DM (PTB‐DM) or without DM (PTB‐NDM); latent TB with DM (LTB‐DM) or without DM (LTB‐NDM) and no TB with DM (NTB‐DM) or without DM (NTB‐NDM) is depicted as pie‐charts. Similarly, frequency distributions of CD8⁺ T‐cell subsets, B‐cell subsets, monocyte subsets and dendritic cell subsets are also depicted.

Figure 3

Summary of the immunological interactions between tuberculosis (TB) and diabetes (DM). The effects of DM on the different arms of the innate and adaptive immune systems is represented by arrows indicating increased or decreased function compared with healthy control individuals.