The immunoregulatory landscape of human tuberculosis granulomas

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…

• NS
  National Science Foundation

  Awards: 5T32AI007290, 2017242837
• UD
  U.S. Department of Defense

  Awards: W81XWH2110143, W81XWH1910235, W81XWH, W81XWH-18-1-0253, W81XWH-18
• BA
  Bill and Melinda Gates Foundation

  Awards: OPP1113682, U19AI057229
• CR
  Cancer Research Institute
• BC
  Breast Cancer Research Foundation
• DR
  Damon Runyon Cancer Research Foundation

  Award: DRG-2292-17
• EM
  European Molecular Biology Organization

  Award: ALTF 1128–2016
• CG
  CRDF Global
• W
  Wellcome
• DR
  Dr. Ralph and Marian Falk Medical Research Trust
• WT
  Wellcome Trust
• NR
  National Research Foundation
• SA
  South African Medical Research Council
• NI
  National Institutes of Health

  Awards: 5DP5OD01982205, 1U24CA22430901, CA246880, R01AI134810, 5R01CA22952904, 5R01AG06827902, U19AI057229, 5T32AI007290, W81XWH, 5R01AG05791504, 5UH3CA24663303, 1R01CA24063801A1, 5U54CA20997105, 5R01AG05628705
• MR
  Medical Research Council
• NC
  National Cancer Institute

  Awards: CA246880-01, 5UH3CA24663303, 1R01CA24063801A1, 5U54CA20997105, 5R01CA22952904, 5T32AI007290, 1U24CA22430901
• NI
  National Institute of Allergy and Infectious Diseases

  Awards: 1U19AI109662, R01AI134810, 5R01AI125197, U19AI057229