The immune landscape in tuberculosis reveals populations linked to disease and latency

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) latently infects approximately one-fourth of the world’s population. The immune mechanisms that govern progression from latent (LTBI) to active pulmonary TB (PTB) remain poorly defined. Experimentally Mtb-infected non-human primates (NHP) mirror the disease observed in humans and recapitulate both PTB and LTBI. We characterized the lung immune landscape in NHPs with LTBI and PTB using high-throughput technologies. Three defining features of PTB in macaque lungs include the influx of plasmacytoid dendritic cells (pDCs), an Interferon (IFN)-responsive macrophage population, and activated T cell responses. In contrast, a CD27+ Natural killer (NK) cell subset accumulated in the lungs of LTBI macaques. This NK cell population was also detected in the circulation of LTBI individuals. This comprehensive analysis of the lung immune landscape will improve the understanding of TB immunopathogenesis, providing potential targets for therapies and vaccines for TB control. [Display omitted] •Characterization of the lung landscape of tuberculosis (TB) latency and disease•Lung CD27+ NK cells are a key feature associated with protection during TB latency•TB disease features lung pDCs, IFN-responsive macrophages, and activated T cells Esaulova, Das, Singh et al. characterize the lung landscape during tuberculosis disease and control using single cell and conventional technologies. Their results delineate NK cells as a feature of protection during latency, and the presence of pDCs, IFN-responsive macrophages and activated T cells as a feature of disease.