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

Abstract

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.

Advances in immune response to pulmonary infection: Nonspecificity, specificity and memory

“…The peripheral blood mononuclear cells (PBMC) of patients with Mycobacterium avium complex‐induced lung disease (MAC‐LD) display a weak response to non‐tuberculous mycobacteria (NTM), with a decreased production of IFN‐γ. The expression of PD‐1 and apoptotic markers, such as TIM‐3, are increased in CD4 + and CD8 + T cells 80 …”

Non-tuberculous mycobacteria lung disease due to Mycobacterium chimaera in a 67-year- old man treated with immune checkpoint inhibitors for lung adenocarcinoma: infection due to dysregulated immunity?

“…The presence of a dysfunctional immune response to NTM, showing the characteristics of immune exhaustion, has been clearly described, thus providing the theoretical explanation for the occurrence of immunopathology among ICI-treated patients during NTM infection. (5) The cases of NTM infections occurring during ICIs therapy and involving the lungs are mainly caused by NTM belonging to Mycobacterium avium complex (MAC) (6). Fujita et al described a possible association between ICI therapy and the development of NTM-LD in three Japanese patients in 2020.…”

Nontuberculous mycobacterial infections during cancer therapy with immune checkpoint inhibitors: a systematic review

“…The presence of a dysfunctional immune response against NTM, showing several features of immune exhaustion, has been clearly described, thus providing the theoretical explanation for the appearance of immunopathology among patients treated with ICIs while infected by NTM. [4] Moreover, ICIs have been even postulated as a possible adjuvant in the treatment of NTM-lung disease (NTM-LD). [5] A case series from Japan in 2020 was the first one reporting three cases of NTM-LD among patients receiving ICIs immunotherapy.…”

“…Still unclear is the role of ICIs therapy on the risk of developing nontuberculous mycobacteria (NTM) infection. The presence of a dysfunctional immune response against NTM, showing several features of immune exhaustion, has been clearly described, thus providing the theoretical explanation for the appearance of immunopathology among patients treated with ICIs while infected by NTM [ 4 ]. Moreover, ICIs have even been postulated as a possible adjuvant in the treatment of NTM-lung disease (NTM-LD) [ 5 ].…”