ArticleImmunity2022
Multimodal profiling of lung granulomas in macaques reveals cellular correlates of tuberculosis control.
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Article in Immunity, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 194 papers.
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194citing papers in PubMed
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Who cites it
194 citing papers in PubMed.
- Early mucosal responses following a randomised controlled human inhaled infection with attenuated Mycobacterium bovis BCG.Nature communications · 2025Trial
- Article
- Host-pathogen interactions in tuberculosis: from immunological mechanisms to translational applications.Cell insight · 2026Review
- Identification of Potential Exosomal miRNA-mRNA Regulatory Network Relevant to Tuberculous-Associated Lung Cancer.Biomedicines · 2026Article
- Host eicosanoid signals define a granuloma fibroblast population that coordinates mycobacterial containment.Cell host & microbe · 2026Article
- BCG vaccination elicits protection against M. tuberculosis infection mediated by two phases of T cell immunity.JCI insight · 2026Article
- γδ T Cells at the Crossroads of Tuberculosis and COPD: From Early Immunity to Tissue Remodeling.International journal of molecular sciences · 2026Review
- Airway immune signatures of protection and disease progression in recent human tuberculosis household contacts.Nature immunology · 2026Article
- A scalable, low-cost, sample hashing workflow for multiomic single-cell analysis using the Seq-Well SNature protocols · 2026Review
- Article
- Immortal genome assumption significantly underestimates replication and death rates ofMicrobiology spectrum · 2026Article
- NETosis associates with human TB lung tissue destruction and disease pathogenesis.EMBO molecular medicine · 2026Article
- The study of immunological markers in tuberculosis across animal models and its translation to human research.Lab animal · 2026Review
- Integrative single-cell profiling and explainable AI identify monocyte-metabolic signatures as diagnostic biomarkers and candidate therapeutic targets in tuberculosis.Archives of microbiology · 2026Article
- Modeling development of tertiary lymphoid structures in pulmonary tuberculosis by 3D profiling and trajectory analysis.bioRxiv : the preprint server for biology · 2026Article
- Immune endotypes in tuberculosis: Keys to decoding disease complexity.Journal of internal medicine · 2026Review
- The host immune response to Mycobacterium tuberculosis determining protection or disease progression.Nature immunology · 2026Review
- Mycobacterium tuberculosis preferentially infects specific macrophage subsets in primate granulomas during the early stages of tuberculosis.Mucosal immunology · 2026Article
- Immortal genome assumption significantly underestimates replication and death rates ofbioRxiv : the preprint server for biology · 2026Article
- SPIC-dependent erythrophagocytic macrophages drive granuloma formation and pathogen persistence during intracellular bacterial infection.bioRxiv : the preprint server for biology · 2026Article
134 more citing papers are in PubMed but not listed here.
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Authors and funding
43 authors.
Hannah P GideonDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA.
Travis K HughesInstitute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Constantine N TzouanasInstitute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Marc H WadsworthInstitute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Ang Andy TuDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Todd M GierahnDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Joshua M PetersRagon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Forrest F HopkinsRagon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Jun-Rong WeiRagon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Conner KummerloweProgram in Computational and Systems Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Nicole L GrantDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Kievershen NarganAfrica Health Research Institute, Durban, South Africa.
Jia Yao PhuahDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
H Jacob BorishDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Pauline MaielloDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Alexander G WhiteDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Caylin G WinchellDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA; Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Sarah K NyquistInstitute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Program in Computational and Systems Biology, Massachusetts Institute of Technology, Cambridge, MA, USA; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA.
Sharie Keanne C GanchuaDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Amy MyersDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Kush V PatelDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Cassaundra L AmeelDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Catherine T CochranDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Samira IbrahimInstitute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Jaime A TomkoDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Lonnie James FryeDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Jacob M RosenbergRagon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.
Angela ShihDivision of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.
Michael ChaoRagon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Edwin KleinDivision of Laboratory Animal Research, University of Pittsburgh, Pittsburgh PA, USA.
Charles A ScangaDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA.
Jose Ordovas-MontanesRagon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Bonnie BergerComputer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA.
Joshua T MattilaCenter for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA; Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
Rajhmun MadanseinDepartment of Cardiothoracic Surgery, University of KwaZulu Natal, Durban, South Africa.
J Christopher LoveRagon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Philana Ling LinCenter for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA; Department of Pediatrics, University of Pittsburgh School of Medicine, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
Alasdair LeslieAfrica Health Research Institute, Durban, South Africa; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa; Department of Infection and Immunity, University College London, London, UK.
Samuel M BeharDepartment of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA.
Bryan BrysonRagon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
JoAnne L FlynnDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: joanne@pitt.edu.
Sarah M FortuneRagon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA. Electronic address: sfortune@hsph.harvard.edu.
Alex K ShalekInstitute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: shalek@mit.edu.
Funding
The impact of HIV viral diversity and cellular immunity on HIV pathogenesisP30AI060354 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI ARTHUR Y KIM · 2004 to 2026
$94.4MVIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Jacqueline A. Lees · 1985 to 2026
$93.9MMolecular Analysis of the Host Immune Response in LeprosyR01AI022553 · NIAID · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ROBERT L MODLIN · 1989 to 2026
$15.7MMultidisciplinary HIV Training ProgramT32AI007387 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI Daniel R. Kuritzkes · 1990 to 2026
$8.8MGraduate Training in Computational and Systems BiologyT32GM087237 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BURGE, CHRISTOPHER B · 2009 to 2023
$4.6MPITT AIDS RESEARCH TRAINING PROGRAMT32AI065380 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BARRATT-BOYES, SIMON M · 2005 to 2020
$3.2MAn integrated multiplexed genomic assay for low input clinical samples1U24AI118672 · NIAID · BROAD INSTITUTE, INC. · PI SHALEK, ALEX K · 2015 to 2019
$2.0MPittsburgh HIV Mentored Training for Investigation of Co-morbidities and Cure (HIV MeTrICC)K12HL143886 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MELLORS, JOHN W, MORRIS, ALISON · 2018 to 2022
$1.7MGhana-SPARCO: Ghana Sickle Pan-African Research ConsortiumU01HL157004 · NHLBI · KWAME NKRUMAH UNIVERSITY/SCIENCE/TECH · PI OFORI-ACQUAH, SOLOMON FIIFI, SARFO, FRED STEPHEN · 2021 to 2025
$1.4MDefining Features of Bacterial Control in M. tuberculosis Granulomas Using Single-cell mRNA SequencingF30AI143160 · NIAID · HARVARD MEDICAL SCHOOL · PI HUGHES, TRAVIS KYLE · 2019 to 2021
$136kNCI NIH HHS P30 CA014051NHLBI NIH HHS K12 HL143886NHLBI NIH HHS U01 HL157004NIAID NIH HHS F30 AI143160NIAID NIH HHS P30 AI060354NIAID NIH HHS R01 AI022553NIAID NIH HHS T32 AI007387NIAID NIH HHS T32 AI065380NIAID NIH HHS U24 AI118672NIGMS NIH HHS T32 GM087237Wellcome TrustWellcome Trust 210662/Z/16/Z
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.
Indexed as
Mycobacterium tuberculosisPulmonary FibrosisTuberculosisAnimalsEcosystemGranulomaLungMacaca fascicularisimmunologyintercellular interactionsMycobacterium tuberculosisPET-CTscRNA-seqsingle-cell RNA sequencingtype 1-type 17type 2 responses
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