Evidence map›Paper›PMID 25653138›Full record

ArticleCellular microbiology2015

Granzyme B-expressing neutrophils correlate with bacterial load in granulomas from Mycobacterium tuberculosis-infected cynomolgus macaques.

Joshua T Mattila, Pauline Maiello, Tao Sun, Laura E Via, JoAnne L Flynn

Open access · greenAbstract read
In one paragraph

Article in Cellular microbiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

49 citing papers in PubMed, 65 citations in OpenAlex.

  1. Cells · 2026
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  13. The Development and Validation of Radiopharmaceuticals Targeting Bacterial Infection.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2023
    Article
  14. Article
  15. Role of phagocyte extracellular traps duringFrontiers in microbiology · 2023
    Review
  16. Article
  17. Exploring the Role of Low-Density Neutrophils DuringFrontiers in cellular and infection microbiology · 2022
    Review
  18. Review
  19. Retention ofACS infectious diseases · 2021
    Article
  20. Immune Cell Degranulation in Fungal Host Defence.Journal of fungi (Basel, Switzerland) · 2021
    Review
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

5 authors at 2 institutions in 1 country.

Joshua T MattilaDepartment of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA, USA.
Pauline MaielloDepartment of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA, USA.
Tao SunDepartment of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.
Laura E ViaTuberculosis Research Section, Laboratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, MD, USA.
JoAnne L FlynnDepartment of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA, USA.
University of Pittsburgh · USNational Institute of Allergy and Infectious Diseases · US

Funding

Experimental Animal Models of TB: Chemotherapeutics and ImagingZIAAI000734 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI BARRY, CLIFTON · 2009 to 2025
$19.6M
International Research in Korea: Clinical Studies of Drug-Resistant TuberculosisZIAAI001067 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI BARRY, CLIFTON · 2009 to 2017
$6.9M
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
Reactivated tuberculosis in SIV-infected cynomolgus macaquesF32AI077183 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MATTILA, JOSHUA T. · 2009 to 2010
$102k
NHLBI NIH HHS HL110811NHLBI NIH HHS R01 HL106804NHLBI NIH HHS R01 HL110811NIAID NIH HHS AI077183NIAID NIH HHS F32 AI077183NIBIB NIH HHS EB012579NIBIB NIH HHS R01 EB012579
6 · The paper itself

Abstract

The role of neutrophils in tuberculosis (TB), and whether neutrophils express granzyme B (grzB), a pro-apoptotic enzyme associated with cytotoxic T cells, is controversial. We examined neutrophils in peripheral blood (PB) and lung granulomas of Mycobacterium tuberculosis-infected cynomolgus macaques and humans to determine whether mycobacterial products or pro-inflammatory factors induce neutrophil grzB expression. We found large numbers of grzB-expressing neutrophils in macaque and human granulomas and these cells contained more grzB+ granules than T cells. Higher neutrophil, but not T cell, grzB expression correlated with increased bacterial load. Although unstimulated PB neutrophils lacked grzB expression, grzB expression increased upon exposure to M.tuberculosis bacilli, M.tuberculosis culture filtrate protein or lipopolysaccharide from Escherichia coli. Perforin is required for granzyme-mediated cytotoxicity by T cells, but was not observed in PB or granuloma neutrophils. Nonetheless, stimulated PB neutrophils secreted grzB as determined by enzyme-linked immunospot assays. Purified grzB was not bactericidal or bacteriostatic, suggesting secreted neutrophil grzB acts on extracellular targets, potentially enhancing neutrophil migration through extracellular matrix and regulating apoptosis or activation in other cell types. These data indicate mycobacterial products and the pro-inflammatory environment of granulomas up-regulates neutrophil grzB expression and suggests a previously unappreciated aspect of neutrophil biology in TB.

Indexed as

Bacterial LoadAnimalsDisease Models, AnimalEnzyme-Linked Immunospot AssayFlow CytometryGene Expression ProfilingGranulomaGranzymesHumansMacaca fascicularisMycobacterium tuberculosisNeutrophilsTuberculosisGranzymes

Identifiers

PMID25653138
PMCPMC4570831
OpenAlexW2147258880

What OpenQuestion holds

Textmetadata
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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.