The immunoregulatory landscape of human tuberculosis granulomas

Erin F. McCaffrey, Michele Donato, Leeat Keren, Zhenghao Chen, Alea Delmastro, Megan B. Fitzpatrick, Sanjana Gupta, Noah F. Greenwald, Alex Baranski, William Graf, Rashmi Kumar, Marc Bosse, Christine Camacho Fullaway, Pratista K. Ramdial, Erna Forgó, Vladimir Jojic, David Van Valen, Smriti Mehra, Shabaana A. Khader, Sean C. BendallMatt van de Rijn, Daniel Kalman, Deepak Kaushal, Robert L. Hunter, Niaz Banaei, Adrie J.C. Steyn, Purvesh Khatri, Michael Angelo

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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.

Original languageEnglish
Pages (from-to)318-329
Number of pages12
JournalNature immunology
Volume23
Issue number2
DOIs
StatePublished - Feb 2022

Fingerprint

Dive into the research topics of 'The immunoregulatory landscape of human tuberculosis granulomas'. Together they form a unique fingerprint.

Cite this