T-cell exhaustion in tuberculosis: pitfalls and prospects

Abstract

T-cells play an important role in immunity but when these cells are overexposed to specific antigens, their function may decline. This state is usually referred to as exhaustion and the T-cells show reduced proliferation and functions such as cytokine release. T-cell exhaustion has been observed in several cancers as well as in chronic infections such as tuberculosis (TB). In chronic Mycobacterium tuberculosis (Mtb) infection, T-cells may express the exhaustion phenotype and show a progressive loss of secretion of IL-2, IFN-γ and TNF-α. In some cancers and chronic infection models, blocking the exhaustion phenotype can be achieved with the so-called checkpoint inhibitors. This results in tumor control and more effective immunity. However, in the case of TB, the T-cell exhaustion results are quite ambiguous. Hence, there is a need to investigate and explain the contribution of checkpoint at a molecular level to the outcome of events in chronic TB. Such information could help to guide the success of new therapies against chronic TB. This review highlights the mechanism through which T-cells undergo exhaustion and the approaches that can avert such events. This will help to design immunotherapies that can reinvigorate T-cell potency to protect patients from TB.

The use of Phyllanthus niruri L. as an immunomodulator for the treatment of infectious diseases in clinical settings

“…T-lymphocytes together with their secreted cytokines that activate macrophage phagocytosis may contribute to the pathology of the disease and are fundamental for effective control of the disease progression [44,45].…”

C‐reactive protein levels in acute respiratory exacerbations of cystic fibrosis

“…9 Loh et al assessed the role on CRP and procalcitonin and erythrocyte sedimentation rate in acute exacerbations of CF. [12][13][14] The WCC rise in this cohort was also minimal. 10 The main finding in our study was that most subjects only had a small rise in their CRP, including patients with pneumonia.…”

IFN‐γ against the 38‐kDa antigen of Mycobacterium tuberculosis discriminates pulmonary tuberculosis from infection and infection from exposure: evidence from a study of human population in a high endemic setting

“…TNFa and IFN-c are pro-inflammatory cytokines produced by Th1 T cells. These two cytokines protect the host against Mtb infection through apoptosis, autophagy, and inflammasome and nitric oxide production (33). However, the fact that different patterns were observed in the three cohort groups may suggest that Mtb uses different mechanisms to suppress the production of these two cytokines in the infected host.…”