Non-tuberculous mycobacteria (NTM) infections are difficult to cure completely with current treatments, and no specific drugs are available. However, recent reports have indicated that immune checkpoint inhibitors may effectively treat pulmonary NTM infections. In this study, we investigated the expression of immune checkpoint molecules in macrophages, the host cells of NTM, and assessed their impact on the microenvironment of infected lesions. Bulk-RNA sequencing and western blot analyses revealed that macrophages infected with Mycobacterium avium, an NTM species, exhibited a pro-inflammatory phenotype and increased PD-L1 expression. Additionally, immunostaining of an NTM-infected mouse model and human tissues showed that increased PD-L1 expression in macrophages was associated with decreased T cell infiltration and increased T cell exhaustion (upregulated PD-1 expression) within infected lesions. These findings suggest that NTM infections evade cellular immunity by enhancing PD-L1 expression in macrophages. Therefore, PD-L1 inhibition may be a promising therapeutic strategy against NTM infections.
© 2025. The Author(s).