Evidence map›Paper›PMID 41489684›Full record

ArticleThe Journal of experimental medicine2026

Single-cell and spatial profiling highlights TB-induced myofibroblasts as drivers of lung pathology.

Ian M Mbano, Nuo Liu, Marc H Wadsworth, Mark J Chambers, Thabo Mpotje, Osaretin E Asowata, Sarah K Nyquist, Kievershen Nargan, Duran Ramsuran, Farina Karim and 20 more

Erratum issuedAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Article
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  4. Article
  5. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors.

Ian M Mbano *Africa Health Research Institute , Durban, South Africa.ORCID 0000-0002-2583-4760
Nuo Liu *Institute for Medical Engineering & Science, Department of Chemistry, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID 0009-0007-0099-3697
Marc H WadsworthInstitute for Medical Engineering & Science, Department of Chemistry, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID 0000-0001-9479-8516
Mark J ChambersAfrica Health Research Institute , Durban, South Africa.ORCID 0000-0002-3712-2752
Thabo MpotjeAfrica Health Research Institute , Durban, South Africa.ORCID 0000-0001-5462-6648
Osaretin E AsowataAfrica Health Research Institute , Durban, South Africa.ORCID 0000-0002-3936-4659
Sarah K NyquistInstitute for Medical Engineering & Science, Department of Chemistry, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID 0000-0002-9045-3665
Kievershen NarganAfrica Health Research Institute , Durban, South Africa.ORCID 0000-0002-4247-981X
Duran RamsuranAfrica Health Research Institute , Durban, South Africa.ORCID 0009-0004-5387-6492
Farina KarimAfrica Health Research Institute , Durban, South Africa.ORCID 0000-0001-9698-016X
Travis K HughesRagon Institute of MGH, MIT, and Harvard , Cambridge, MA, USA.ORCID 0000-0001-8291-8672
Joshua D BromleyInstitute for Medical Engineering & Science, Department of Chemistry, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID 0000-0001-8692-2740
Robert KrauseAfrica Health Research Institute , Durban, South Africa.ORCID 0000-0003-1558-0397
Threnesan NaidooAfrica Health Research Institute , Durban, South Africa.ORCID 0000-0002-1864-4301
Liku B TezeraNIHR Biomedical Research Centre, School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton , Southampton, UK.ORCID 0000-0002-7898-6709
Michaela T ReichmannNIHR Biomedical Research Centre, School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton , Southampton, UK.ORCID 0000-0002-3015-9827
Sharie Keanne GanchuaDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0003-1577-5055
Henrik N KløverprisAfrica Health Research Institute , Durban, South Africa.ORCID 0000-0002-2165-3313
Kaylesh J DullabhSchool of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.ORCID 0000-0002-2469-871X
Rajhmun MadanseinSchool of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.ORCID 0000-0001-7306-1304
Sergio TrianaInstitute for Medical Engineering & Science, Department of Chemistry, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID 0000-0003-0370-7821
Adrie J C SteynAfrica Health Research Institute , Durban, South Africa.ORCID 0000-0001-9177-8827
Bonnie BergerProgram in Health Sciences & Technology, Harvard Medical School and Massachusetts Institute of Technology , Boston, MA, USA.ORCID 0000-0002-2724-7228
Mohlopheni J MarakalalaAfrica Health Research Institute , Durban, South Africa.ORCID 0000-0001-7476-1652
Gabriele PollaraDepartment of Infection and Immunity, University College London, UK.
Sarah M FortuneRagon Institute of MGH, MIT, and Harvard , Cambridge, MA, USA.ORCID 0000-0001-7565-9975
JoAnne L FlynnDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0001-7874-8981
Paul T Elkington *NIHR Biomedical Research Centre, School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton , Southampton, UK.ORCID 0000-0003-0390-0613
Alex K Shalek *Institute for Medical Engineering & Science, Department of Chemistry, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID 0000-0001-5670-8778
Alasdair Leslie *Africa Health Research Institute , Durban, South Africa.ORCID 0000-0003-2538-6467

Funding

IMMUNE MECHANISMS OF PROTECTION AGAINST MYCOBACTERIUM TUBERCULOSIS CENTER (IMPAC-TB)75N93019C00071 · NIAID · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI FORTUNE, SARAH · 2019 to 2025
$57.3M
Bill and Melinda Gates Foundation OPP1137006Medical Research Council MR CF2021-2\126Medical Research Council MR/W025728/1NIAID NIH HHS 75N93019C00071NIH HHS 75N93019C00071SANTHE DELTAS Africa Initiative DEL-15-006Wellcome TrustWellcome Trust 201433/A/16/AWellcome Trust 210662/Z/18/Z
6 · The paper itself

Abstract

Tuberculosis (TB) typically causes lung destruction and fibrosis, leading to ∼1.3 million deaths annually. The cellular drivers of human TB immunopathology remain poorly defined. We performed single-cell RNA sequencing and spatial transcriptomics on lung tissues from TB-infected and TB-negative individuals, identifying 30 distinct immune, parenchymal, and stromal cell subsets. Several were linked to TB pathology and corroborated through immunohistochemistry, flow cytometry, and independent human datasets. Fibroblasts were identified as major drivers in both active TB granuloma and TB-diseased lung tissue. In particular, the MMP1+CXCL5+ fibroblast subset, expressing a myofibroblast-like gene signature, was associated with severe disease and higher bacterial burden in nonhuman primate granulomas. Network analyses revealed cross talk between MMP1+CXCL5+ fibroblasts and SPP1+ macrophages within the granuloma cuff, which has been reported in other disease contexts, and may play an important role in TB immunopathology. Our findings highlight previously unappreciated cell populations and potential targets for novel TB therapies.

Indexed as

LungMyofibroblastsSingle-Cell AnalysisTuberculosis, PulmonaryAnimalsFemaleFibroblastsGene Expression ProfilingGranulomaHumansMacrophagesMaleMycobacterium tuberculosisTranscriptome

Identifiers

PMID41489684
PMCPMC12767585

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.