Abstract
Immune exhaustion is a condition associated with chronic infections and cancers, characterized by the inability of antigen-specific T cells to eliminate the cognate antigen. Exhausted T cells display a peculiar phenotypic profile and exclusive functional characteristics. Immune exhaustion has been described in patients with Mycobacterium tuberculosis infection, and cases of tuberculosis reactivation have been reported in those treated with immune checkpoint inhibitors, drugs able to re-establish T-cells’ function. Exhausted T CD8+ cells’ profile has also been described in patients with infection due to nontuberculous mycobacteria. In this review, we initially provide an overview of the mechanisms leading to immune exhaustion in patients infected by Mycobacterium tuberculosis and nontuberculous mycobacteria. We then dissect the therapeutic perspectives related to immune checkpoint blockade in patients with these infections.
Highlights
Tuberculosis (TB) is an ancient and, extensively studied infectious disease caused by mycobacteria grouped in the Mycobacterium tuberculosis complex, among whichMycobacterium tuberculosis sensu stricto is the principal driver of the current global burden
We aim to provide an overview of the interaction between the immune system, Mtb, and Nontuberculous mycobacteria (NTM), focusing on the condition of immune exhaustion (IE)
IE is and which mechanisms lead to it, we describe the current evidence on how IE relates to Mtb and NTM infection and possible therapeutic approaches aiming at reverting IE to increase pathogens’ clearance and, eventually, improve the clinical outcome
Summary
Tuberculosis (TB) is an ancient and, extensively studied infectious disease caused by mycobacteria grouped in the Mycobacterium tuberculosis complex, among which. Their incidence is growing, ranging from 8.6 to 17.7 cases per 100,000 personyears, and has surpassed that of Mtb in Western countries [2,3] Their ability to cause disease in the immunocompetent has been acknowledged, and several risk factors have been identified, with pre-existing structural lung disease, genetically determined defects of cell-mediated immunity, oral corticosteroid treatment, chronic renal failure, and diabetes mellitus among the most relevant [4]. Both Mtb and NTM are intracellular pathogens that can produce a chronic infection requiring an efficacious and coordinated T-cell response to eliminate the microorganism. IE is and which mechanisms lead to it, we describe the current evidence on how IE relates to Mtb and NTM infection and possible therapeutic approaches aiming at reverting IE to increase pathogens’ clearance and, eventually, improve the clinical outcome (i.e., immune checkpoint inhibitors)
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