Evidence map›Paper›PMID 24815353›Full record

ArticleThe American journal of pathology2014

Characterization of a novel necrotic granuloma model of latent tuberculosis infection and reactivation in mice.

Noton K Dutta, Peter B Illei, Sanjay K Jain, Petros C Karakousis

Open access · bronzeAbstract read
In one paragraph

Article in The American journal of pathology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
4.9field-weighted citation impact, top 4% of its field
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

38 citing papers in PubMed, 55 citations in OpenAlex.

  1. Article
  2. Crosstalk betweenFrontiers in immunology · 2026
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  3. Review
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  5. Microorganisms · 2022
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  7. CWHM-12, an Antagonist of Integrin-Mediated Transforming Growth Factor-Beta Activation Confers Protection During EarlyJournal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2022
    Article
  8. Article
  9. Article
  10. Review
  11. Targeting Non-ReplicatingInternational journal of molecular sciences · 2021
    Review
  12. Article
  13. One Size Fits All? Not inFrontiers in cellular and infection microbiology · 2021
    Review
  14. Review
  15. Pathogens (Basel, Switzerland) · 2020
    Article
  16. Article
  17. Article
  18. Article
  19. Vaccine strategies for theNPJ vaccines · 2020
    Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Noton K DuttaDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Peter B IlleiDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Sanjay K JainDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Petros C KarakousisDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. Electronic address: petros@jhmi.edu.
Johns Hopkins University · USJohns Hopkins Medicine · US

Funding

A Multidisciplinary Approach to Understanding TB Latency and ReactivationR01HL106786 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI BADER, JOEL S., KARAKOUSIS, PETROS C · 2010 to 2013
$3.1M
Novel imaging biomarkers to address fundamental controversies in TB pathogenesisDP2OD006492 · OD · JOHNS HOPKINS UNIVERSITY · PI JAIN, SANJAY · 2009 to 2014
$2.9M
Regulatory networks involved in Mycobacterium tuberculosis persistenceR01AI083125 · NIAID · JOHNS HOPKINS UNIVERSITY · PI KARAKOUSIS, PETROS C · 2009 to 2013
$2.7M
NHLBI NIH HHS R01 HL106786NHLBI NIH HHS R01HL106786NIAID NIH HHS R01 AI083125NIAID NIH HHS R01AI083125NIH HHS DP2 OD006492
6 · The paper itself

Abstract

We sought to develop and characterize a novel paucibacillary model in mice, which develops necrotic lung granulomas after infection with Mycobacterium tuberculosis. Six weeks after aerosol immunization with recombinant Mycobacterium bovis bacillus Calmette-Guerin overexpressing the 30-kDa antigen, C3HeB/FeJ mice were aerosol infected with M. tuberculosis H37Rv. Six weeks later, mice were treated with one of three standard regimens for latent tuberculosis infection or tumor necrosis factor (TNF)-neutralizing antibody. Mouse lungs were analyzed by histological features, positron emission tomography/computed tomography, whole-genome microarrays, and RT-PCR. Lungs and sera were studied by multiplex enzyme-linked immunosorbent assays. Paucibacillary infection was established, recapitulating the sterilizing activities of human latent tuberculosis infection regimens. TNF neutralization led to increased lung bacillary load, disrupted granuloma architecture with expanded necrotic foci and reduced tissue hypoxia, and accelerated animal mortality. TNF-neutralized mouse lungs and sera showed significant up-regulation of interferon γ, IL-1β, IL-6, IL-10, chemokine ligands 2 and 3, and matrix metalloproteinase genes. Clinical and microbiological reactivation of paucibacillary infection by TNF neutralization was associated with reduced hypoxia in lung granulomas and induction of matrix metalloproteinases and proinflammatory cytokines. This model may be useful for screening the sterilizing activity of novel anti-tuberculosis drugs, and identifying mycobacterial regulatory and metabolic pathways required for bacillary growth restriction and reactivation.

Indexed as

Disease Models, AnimalAnimalsAntibodies, NeutralizingCytokinesFemaleGranulomaLatent TuberculosisLungMice, Inbred C3HNecrosisTranscriptomeTumor Necrosis Factor-alphaAntibodies, NeutralizingCytokinesTumor Necrosis Factor-alpha

Identifiers

PMID24815353
PMCPMC4076462
OpenAlexW1988214988

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.