@article{4b4e26f98461485b96f251e65d998472,
title = "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.",
author = "McCaffrey, {Erin F.} and Michele Donato and Leeat Keren and Zhenghao Chen and Alea Delmastro and Fitzpatrick, {Megan B.} and Sanjana Gupta and Greenwald, {Noah F.} and Alex Baranski and William Graf and Rashmi Kumar and Marc Bosse and Fullaway, {Christine Camacho} and Ramdial, {Pratista K.} and Erna Forg{\'o} and Vladimir Jojic and {Van Valen}, David and Smriti Mehra and Khader, {Shabaana A.} and Bendall, {Sean C.} and {van de Rijn}, Matt and Daniel Kalman and Deepak Kaushal and Hunter, {Robert L.} and Niaz Banaei and Steyn, {Adrie J.C.} and Purvesh Khatri and Michael Angelo",
note = "Funding Information: We thank T. Risom, D. Glass, M. Carter, J. Mattila, J. Flynn and A. Kasmar for discussions and comments. We thank P. Chu and the Stanford Human Histology Core for providing technical assistance. E.F.M. was supported by the National Science Foundation (graduate research fellowship grant 2017242837) and training grant 5T32AI007290. L.K. was a Damon Runyon Fellow supported by the Damon Runyon Cancer Research Foundation (DRG-2292-17) and a nonstipendiary awardee of the EMBO long-term fellowship (ALTF 1128–2016). N.F.G. was supported by the National Cancer Institute (grant CA246880-01) and Stanford University (graduate fellowship). A.J.C.S. was supported by the National Institutes of Health (grants R61/33AI138280 and R01AI134810), CRDF Global, the South African Medical Research Council and a National Research Foundation BRICS multilateral grant. P.K. was funded in part by the Bill and Melinda Gates Foundation (OPP1113682), the National Institute of Allergy and Infectious Diseases (grants 1U19AI109662, U19AI057229 and 5R01AI125197), the Department of Defense (contracts W81XWH-18-1-0253 and W81XWH1910235) and the Ralph & Marian Falk Medical Research Trust. M.A. was supported by the National Institutes of Health (grants 5U54CA20997105, 5DP5OD01982205, 1R01CA24063801A1, 5R01AG06827902, 5UH3CA24663303, 5R01CA22952904, 1U24CA22430901, 5R01AG05791504 and 5R01AG05628705), the Department of Defense (contracts W81XWH2110143), the Wellcome Trust and other funding from the Bill and Melinda Gates Foundation, Cancer Research Institute, the Parker Center for Cancer Immunotherapy and the Breast Cancer Research Foundation. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = feb,
doi = "10.1038/s41590-021-01121-x",
language = "English",
volume = "23",
pages = "318--329",
journal = "Nature Immunology",
issn = "1529-2908",
number = "2",
}