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 Bendall; Matt van de Rijn; Daniel Kalman; Deepak Kaushal; Robert L Hunter; Niaz Banaei; Adrie J C Steyn; Purvesh Khatri; Michael Angelo

doi:10.1038/s41590-021-01121-x

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

Department of Molecular Cell Biology

Weizmann Institute of Science

Research output: Contribution to journal › Article › peer-review

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 language	English
Pages (from-to)	318-329
Number of pages	12
Journal	Nature Immunology
Volume	23
Issue number	2
Early online date	20 Jan 2022
DOIs	https://doi.org/10.1038/s41590-021-01121-x
State	Published - Feb 2022

All Science Journal Classification (ASJC) codes

Immunology and Allergy
Immunology

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McCaffrey, E. F., Donato, M., Keren, L., Chen, Z., Delmastro, A., Fitzpatrick, M. B., Gupta, S., Greenwald, N. F., Baranski, A., Graf, W., Kumar, R., Bosse, M., Fullaway, C. C., Ramdial, P. K., Forgó, E., Jojic, V., Van Valen, D., Mehra, S., Khader, S. A., ... Angelo, M. (2022). The immunoregulatory landscape of human tuberculosis granulomas. Nature Immunology, 23(2), 318-329. https://doi.org/10.1038/s41590-021-01121-x

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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 = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = feb,

doi = "10.1038/s41590-021-01121-x",

language = "الإنجليزيّة",

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McCaffrey, EF, Donato, M, Keren, L, Chen, Z, Delmastro, A, Fitzpatrick, MB, Gupta, S, Greenwald, NF, Baranski, A, Graf, W, Kumar, R, Bosse, M, Fullaway, CC, Ramdial, PK, Forgó, E, Jojic, V, Van Valen, D, Mehra, S, Khader, SA, Bendall, SC, van de Rijn, M, Kalman, D, Kaushal, D, Hunter, RL, Banaei, N, Steyn, AJC, Khatri, P & Angelo, M 2022, 'The immunoregulatory landscape of human tuberculosis granulomas', Nature Immunology, vol. 23, no. 2, pp. 318-329. https://doi.org/10.1038/s41590-021-01121-x

TY - JOUR

T1 - The immunoregulatory landscape of human tuberculosis granulomas

AU - McCaffrey, Erin F

AU - Donato, Michele

AU - Keren, Leeat

AU - Chen, Zhenghao

AU - Delmastro, Alea

AU - Fitzpatrick, Megan B

AU - Gupta, Sanjana

AU - Greenwald, Noah F

AU - Baranski, Alex

AU - Graf, William

AU - Kumar, Rashmi

AU - Bosse, Marc

AU - Fullaway, Christine Camacho

AU - Ramdial, Pratista K

AU - Forgó, Erna

AU - Jojic, Vladimir

AU - Van Valen, David

AU - Mehra, Smriti

AU - Khader, Shabaana A

AU - Bendall, Sean C

AU - van de Rijn, Matt

AU - Kalman, Daniel

AU - Kaushal, Deepak

AU - Hunter, Robert L

AU - Banaei, Niaz

AU - Steyn, Adrie J C

AU - Khatri, Purvesh

AU - Angelo, Michael

PY - 2022/2

Y1 - 2022/2

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85123192347&partnerID=8YFLogxK

U2 - 10.1038/s41590-021-01121-x

DO - 10.1038/s41590-021-01121-x

M3 - مقالة

C2 - 35058616

SN - 1529-2908

VL - 23

SP - 318

EP - 329

JO - Nature Immunology

JF - Nature Immunology

IS - 2

ER -

The immunoregulatory landscape of human tuberculosis granulomas

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