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 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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 20, 2022
- Source ID
- 10.1038/s41590-021-01121-x
Entities
People
- Adrie J C Steyn
- Alea Delmastro
- Alex Baranski
- Christine Camacho Fullaway
- Daniel Kalman
- David Van Valen
- Deepak Kaushal
- Erin McCaffrey
- Erna Forgó
- Leeat Keren
- Marc Bosse
- Matt Van De Rijn
- Megan B Fitzpatrick
- Michael Angelo
- Michele Donato
- Niaz Banaei
- Noah F Greenwald
- Pratista K. Ramdial
- Purvesh Khatri
- Rashmi Kumar
- Robert L. Hunter
- Sanjana Gupta
- Sean C Bendall
- Shabaana A Khader
- Smriti Mehra
- Vladimir Jojic
- William D. Graf
- Zhenghao Chen
Organizations
- CRDF Global
- Cancer Research Institute
- Damon Runyon Cancer Research Foundation
- Dr. Ralph and Marian Falk Medical Research Trust
- European Molecular Biology Organization
- Gates Foundation
- National Cancer Institute
- National Institute of Allergy and Infectious Diseases
- National Institutes of Health
- National Science Foundation
- South African Medical Research Council
- United States Department of Defense
- Wellcome Trust