T-Cell Exhaustion in Mycobacterium tuberculosis and Nontuberculous Mycobacteria Infection: Pathophysiology and Therapeutic Perspectives

Lombardi, Andrea; Villa, Simone; Castelli, Valeria; Bandera, Alessandra; Gori, Andrea

doi:10.3390/microorganisms9122460

Cited by 31 publications

(26 citation statements)

References 60 publications

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“…T cell exhaustion happens in chronic infections with lymphocytic choriomeningitis virus (LCMV), hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) and Mycobacterium tuberculosis (M. tuberculosis). 1,3,34 Continuous antigen stimulation, high levels of reactive oxygen species (ROS) and hypoxia drive T cell exhaustion. 35 Considering exhausted CD4 + T cells are heterogeneous, 36 the exhausted T cells mentioned in this article mainly refer to exhausted CD8 + T cells.…”

Section: The Metabolic Requirements Of Exhausted T Cellsmentioning

confidence: 99%

Metabolic plasticity and regulation of T cell exhaustion

Liu

Zhang

et al. 2022

Immunology

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The metabolic reprogramming during T cell activation and differentiation affects T cell fate and immune responses. Cell metabolism may serve as the driving force that induces epigenetic modifications, contributing to regulating T cell differentiation. Persistent pathogen infection leads to T cell exhaustion, which is composed of two main subsets and with distinct metabolic characteristics. The progenitor exhausted T cells utilize mitochondrial fatty acid oxidation (FAO) and oxidative phosphorylation (OXPHOS) for energy, while terminally exhausted T cells mainly rely on glycolytic metabolism with impaired glycolysis and OXPHOS. Here, we compiled the latest research on how T cell metabolism defines differentiation, focusing on T cell exhaustion during chronic infections. In addition, metabolicrelated factors including antigen stimulation signals strength, cytokines and epigenetics affecting T cell exhaustion were also reviewed. Furthermore, the intervention strategies on metabolism and epigenetics to reverse T cell exhaustion were discussed in detail, which may contribute to achieving the goal of prevention and treatment of T cell exhaustion.

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Section: The Metabolic Requirements Of Exhausted T Cellsmentioning

confidence: 99%

Metabolic plasticity and regulation of T cell exhaustion

Liu

Zhang

et al. 2022

Immunology

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“…Secondly, NTM disease is associated with suppressed T-cell-mediated response. Previous studies suggested that patients with NTM disease have lower counts of CD4 + T cells, as well as a higher apoptosis rate on CD4 + lymphocytes compared to healthy donors ( 23 , 24 ). NTM are opportunistic human pathogens that colonize macrophages ( 25 ).…”

Section: Discussionmentioning

confidence: 95%

Central nervous system infection caused by Mycobacterium houstonense: A case report

Wang

Wang²,

Yang³

et al. 2022

Front. Neurol.

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BackgroundMycobacterium houstonense is a rapidly growing mycobacterium (RGM) that belongs to the unnamed third biovariant complex of the Mycobacterium fortuitum group, which is rarely responsible for human infection. Approximately 76% of infections caused by the M. fortuitum group occur after open fractures or skin, soft tissue, bone, or puncture wounds. To date, only a few cases of human infectious disease caused by M. houstonense have been reported worldwide.Case presentationWe present a case of a 26-year-old man with a central nervous system (CNS) infection caused by M. houstonense. The patient was transferred to our hospital because of headaches and muscle strength changes. One month prior to presentation at our hospital, the patient was diagnosed with tuberculous meningitis at the other two hospitals, but his condition did not improve after anti-tuberculous treatment, antibiotics, and anti-viral treatment before admission to our hospital. Lumbar puncture was performed at both previous hospitals, as well as at our hospital; the results consistently indicated high cerebrospinal fluid (CSF) opening pressure. M. houstonense was detected in the CSF of the second hospital's lumbar puncture by metagenomic next-generation sequencing (mNGS) but was not identified at our hospital. The patient was discharged from our hospital after receiving non-tuberculous mycobacterium (NTM) treatment for 1 month according to the Chinese NTM guidelines. However, the patient died 20 days after discharge.ConclusionSince it is difficult to identify M. houstonense, this is the first case of human CNS infection caused by M. houstonense in China. This case may be considered by neurologists and infectious physicians when CNS infection does not respond to conventional treatment, especially in the uncommon type of NTM.

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“…Taken together, these data suggest that lymphocytes IE is recognizable during NTM-LD and that it has a crucial, yet not completely understood, role in the disease. Future research should address its possible employment as prognostic/predictive factor and the coadministration of immune checkpoint inhibitors with standard antibacterial therapy in order to achieve quickly and in a more stable manner the control of the disease ( 82 ).…”

Section: Conventional T Cells and Immune Exhaustionmentioning

confidence: 99%

Innate and Adaptive Lymphocytes in Non-Tuberculous Mycobacteria Lung Disease: A Review

et al. 2022

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Non-tuberculous mycobacteria (NTM) are ubiquitous environmental microorganisms capable of a wide range of infections that primarily involve the lymphatic system and the lower respiratory tract. In recent years, cases of lung infection sustained by NTM have been steadily increasing, due mainly to the ageing of the population with underlying lung disease, the enlargement of the cohort of patients undergoing immunosuppressive medications and the improvement in microbiologic diagnostic techniques. However, only a small proportion of individuals at risk ultimately develop the disease due to reasons that are not fully understood. A better understanding of the pathophysiology of NTM pulmonary disease is the key to the development of better diagnostic tools and therapeutic targets for anti-mycobacterial therapy. In this review, we cover the various types of interactions between NTM and lymphoid effectors of innate and adaptive immunity. We also give a brief look into the mechanism of immune exhaustion, a phenomenon of immune dysfunction originally reported for chronic viral infections and cancer, but recently also observed in the setting of mycobacterial diseases. We try to set the scene to postulate that a better knowledge of immune exhaustion can play a crucial role in establishing prognostic/predictive factors and enabling a broader investigation of immune-modulatory drugs in the experimental treatment of NTM pulmonary disease.

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T-Cell Exhaustion in Mycobacterium tuberculosis and Nontuberculous Mycobacteria Infection: Pathophysiology and Therapeutic Perspectives

Cited by 31 publications

References 60 publications

Metabolic plasticity and regulation of T cell exhaustion

Metabolic plasticity and regulation of T cell exhaustion

Central nervous system infection caused by Mycobacterium houstonense: A case report

Innate and Adaptive Lymphocytes in Non-Tuberculous Mycobacteria Lung Disease: A Review

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