Evidence map›Paper›PMID 25368116›Full record

ArticleInfection and immunity2015

Macrophage polarization drives granuloma outcome during Mycobacterium tuberculosis infection.

Simeone Marino, Nicholas A Cilfone, Joshua T Mattila, Jennifer J Linderman, JoAnne L Flynn, Denise E Kirschner

Open access · bronzeAbstract read
In one paragraph

Article in Infection and immunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.

0numbers the graph read from it
0cells of the map it votes in
113citing papers in PubMed
7.7field-weighted citation impact, top 2% 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

113 citing papers in PubMed, 191 citations in OpenAlex.

  1. Article
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  5. Participation of miRNA-23a-3p in Pulmonary Tuberculosis Through Macrophages via the JAK-STAT Pathway.International journal of chronic obstructive pulmonary disease · 2026
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  8. ThemSphere · 2025
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  12. Journal of bacteriology · 2025
    Review
  13. Review
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  15. Article
  16. Building Spatiotemporal Understanding ofACS infectious diseases · 2025
    Review
  17. Epigenetic Mechanisms Induced byInternational journal of molecular sciences · 2024
    Review
  18. Article
  19. Article
  20. MedComm · 2024
    Review

53 more citing papers are in PubMed but not listed here.

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

6 authors at 2 institutions in 1 country.

Simeone MarinoDepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Nicholas A CilfoneDepartment of Chemical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Joshua T MattilaDepartment of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Jennifer J LindermanDepartment of Chemical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
JoAnne L FlynnDepartment of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Denise E KirschnerDepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA kirschne@umich.edu.
University of Michigan–Ann Arbor · USUniversity of Pittsburgh · US

Funding

Predicting immune responses that correlate with protection against tuberculosisR01HL110811 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FLYNN, JOANNE L., KIRSCHNER, DENISE E · 2012 to 2016
$5.9M
Defining how the spectrum of latency affects reactivation of TBR01HL106804 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FLYNN, JOANNE L., KIRSCHNER, DENISE E · 2010 to 2013
$2.6M
A multi-scale model to predict outcomes of immunomodulation and drug therapy duriR01EB012579 · NIBIB · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI FLYNN, JOANNE L., KIRSCHNER, DENISE E · 2011 to 2014
$2.3M
NHLBI NIH HHS R01 HL 106804NHLBI NIH HHS R01 HL106804NHLBI NIH HHS R01 HL 110811NHLBI NIH HHS R01 HL110811NIBIB NIH HHS R01 EB012579
6 · The paper itself

Abstract

Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), induces formation of granulomas, structures in which immune cells and bacteria colocalize. Macrophages are among the most abundant cell types in granulomas and have been shown to serve as both critical bactericidal cells and targets for M. tuberculosis infection and proliferation throughout the course of infection. Very little is known about how these processes are regulated, what controls macrophage microenvironment-specific polarization and plasticity, or why some granulomas control bacteria and others permit bacterial dissemination. We take a computational-biology approach to investigate mechanisms that drive macrophage polarization, function, and bacterial control in granulomas. We define a "macrophage polarization ratio" as a metric to understand how cytokine signaling translates into polarization of single macrophages in a granuloma, which in turn modulates cellular functions, including antimicrobial activity and cytokine production. Ultimately, we extend this macrophage ratio to the tissue scale and define a "granuloma polarization ratio" describing mean polarization measures for entire granulomas. Here we coupled experimental data from nonhuman primate TB granulomas to our computational model, and we predict two novel and testable hypotheses regarding macrophage profiles in TB outcomes. First, the temporal dynamics of granuloma polarization ratios are predictive of granuloma outcome. Second, stable necrotic granulomas with low CFU counts and limited inflammation are characterized by short NF-κB signal activation intervals. These results suggest that the dynamics of NF-κB signaling is a viable therapeutic target to promote M1 polarization early during infection and to improve outcome.

Indexed as

AnimalsComputer SimulationDisease Models, AnimalGranulomaMacaca fascicularisMacrophagesNF-kappa BTuberculosisNF-kappa B

Identifiers

PMID25368116
PMCPMC4288886
OpenAlexW2068034671

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.