2022/01/20 by Erin McCaffrey, Michele Donato, Leeat Keren +25 · 1 voice · 1 citation
Medicine · #Tuberculosis Research and Epidemiology #Infectious Diseases and Tuberculosis #Sarcoidosis and Beryllium Toxicity Research
paper · pdf · doi:10.1038/s41590-021-01121-x
openalex publication_date 2022/01/20 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
Abstract Tuberculosis (TB) in humans is characterized by formation of immune-rich granulomas in infected tissues, the architecture and composition of which are thought to affect disease outcome. However, our understanding of the spatial relationships that control human granulomas is limited. Here, we used multiplexed ion beam imaging by time of flight (MIBI-TOF) to image 37 proteins in tissues from patients with active TB. We constructed a comprehensive atlas that maps 19 cell subsets across 8 spatial microenvironments. This atlas shows an IFN-γ-depleted microenvironment enriched for TGF-β, regulatory T cells and IDO1 + PD-L1 + myeloid cells. In a further transcriptomic meta-analysis of peripheral blood from patients with TB, immunoregulatory trends mirror those identified by granuloma imaging. Notably, PD-L1 expression is associated with progression to active TB and treatment response. These data indicate that in TB granulomas, there are local spatially coordinated immunoregulatory programs with systemic manifestations that define active TB.