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Multimodal profiling of lung granulomas in macaques reveals cellular correlates of tuberculosis control

Gideon, Hannah P; Hughes, Travis K; Tzouanas, Constantine N; Wadsworth, Marc H; Tu, Ang Andy; Gierahn, Todd M; Peters, Joshua M; ... Shalek, Alex K; + view all (2022) Multimodal profiling of lung granulomas in macaques reveals cellular correlates of tuberculosis control. Immunity , 55 (5) 827-846.e10. 10.1016/j.immuni.2022.04.004. Green open access

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Abstract

Mycobacterium tuberculosis lung infection results in a complex multicellular structure: the granuloma. In some granulomas, immune activity promotes bacterial clearance, but in others, bacteria persist and grow. We identified correlates of bacterial control in cynomolgus macaque lung granulomas by co-registering longitudinal positron emission tomography and computed tomography imaging, single-cell RNA sequencing, and measures of bacterial clearance. Bacterial persistence occurred in granulomas enriched for mast, endothelial, fibroblast, and plasma cells, signaling amongst themselves via type 2 immunity and wound-healing pathways. Granulomas that drove bacterial control were characterized by cellular ecosystems enriched for type 1-type 17, stem-like, and cytotoxic T cells engaged in pro-inflammatory signaling networks involving diverse cell populations. Granulomas that arose later in infection displayed functional characteristics of restrictive granulomas and were more capable of killing Mtb. Our results define the complex multicellular ecosystems underlying (lack of) granuloma resolution and highlight host immune targets that can be leveraged to develop new vaccine and therapeutic strategies for TB.

Type: Article
Title: Multimodal profiling of lung granulomas in macaques reveals cellular correlates of tuberculosis control
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.immuni.2022.04.004
Publisher version: https://doi.org/10.1016/j.immuni.2022.04.004
Language: English
Additional information: © 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Mycobacterium tuberculosis, immunology, single-cell RNA sequencing, scRNA-seq, PET-CT, type 1-type 17, type 2 responses, intercellular interactions
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10183814
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