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Researchers used MIBI™ spatial proteomics technology to reveal new clues about tuberculosis, laying the groundwork for future clinical biomarkers that could potentially lead to better outcomes for patients.

The immunoregulatory landscape of human tuberculosis granulomas

McCaffrey, et al., Nature Immunology February 2022

Key Insights
  • Scientists constructed a comprehensive TB granuloma tissue atlas with cell lineage, functional state, and spatial distribution information
  • MIBI technology allowed the team to analyze archival FFPE samples, making it possible to study a dangerous pathogen without the need for a BSL-3 lab
  • The team analyzed dozens of biomarkers simultaneously, enabling them to profile 19 distinct cell subsets and map them to eight phenotypically different granuloma microenvironments with varying roles in TB
  • A comparison to gene expression data from studies of more than 1,500 TB patients revealed that granuloma biology patterns identified in this analysis mirrored those in patients’ blood, indicating a path to developing clinical biomarkers

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 (MIBI) 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.

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