Evidence map›Paper›PMID 34111032›Full record

Trial reportThe Journal of clinical investigation2021

Monocyte metabolic transcriptional programs associate with resistance to tuberculin skin test/interferon-γ release assay conversion.

Jason D Simmons, Phu T Van, Catherine M Stein, Violet Chihota, Thobani Ntshiqa, Pholo Maenetje, Glenna J Peterson, Anthony Reynolds, Penelope Benchek, Kavindhran Velen and 11 more

Open access · bronzeAbstract readClinical TrialMulticenter Study
In one paragraph

Trial report in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.4field-weighted citation impact, top 15% 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

21 citing papers in PubMed, 29 citations in OpenAlex.

  1. Review
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  4. A proteome-wide atlas of humoral immunity toFrontiers in immunology · 2026
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  13. Specific CD4Nature immunology · 2024
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  15. Frontiers in immunology · 2024
    Article
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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

21 authors at 6 institutions in 4 countries.

Jason D SimmonsTB Research and Training Center, Department of Medicine, University of Washington, Seattle, Washington, USA.
Phu T VanFred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Catherine M SteinDepartment of Population & Quantitative Health Sciences and.
Violet ChihotaSchool of Public Health, University of Witwatersrand, Johannesburg, South Africa.
Thobani NtshiqaThe Aurum Institute, Parktown, South Africa.
Pholo MaenetjeThe Aurum Institute, Parktown, South Africa.
Glenna J PetersonTB Research and Training Center, Department of Medicine, University of Washington, Seattle, Washington, USA.
Anthony ReynoldsTB Research and Training Center, Department of Medicine, University of Washington, Seattle, Washington, USA.
Penelope BenchekDepartment of Population & Quantitative Health Sciences and.
Kavindhran VelenThe Aurum Institute, Parktown, South Africa.
Katherine L FieldingSchool of Public Health, University of Witwatersrand, Johannesburg, South Africa.
Alison D GrantSchool of Public Health, University of Witwatersrand, Johannesburg, South Africa.
Andrew D GrausteinTB Research and Training Center, Department of Medicine, University of Washington, Seattle, Washington, USA.
Felicia K NguyenTB Research and Training Center, Department of Medicine, University of Washington, Seattle, Washington, USA.
Chetan SeshadriTB Research and Training Center, Department of Medicine, University of Washington, Seattle, Washington, USA.
Raphael GottardoFred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Harriet Mayanja-KizzaDepartment of Medicine, School of Medicine, Makerere University, Kampala, Uganda.
Robert S WallisThe Aurum Institute, Parktown, South Africa.
Gavin ChurchyardThe Aurum Institute, Parktown, South Africa.
W Henry BoomDepartment of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
Thomas R HawnTB Research and Training Center, Department of Medicine, University of Washington, Seattle, Washington, USA.
University of Washington · USAurum Institute · ZAUniversity of the Witwatersrand · ZACase Western Reserve University · USFred Hutch Cancer Center · USMakerere University · UG

Funding

HOST DEFENSE TRAINING IN ALLERGY AND INFECTIOUS DISEASEST32AI007044 · NIAID · UNIVERSITY OF WASHINGTON · PI DAVID Neal FREDRICKS · 1985 to 2026
$14.6M
Resistance to MTB infection in HIV infected individuals in Uganda and S. AfricaR01AI124348 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI BOOM, W. HENRY, HAWN, THOMAS R · 2016 to 2020
$11.3M
Aurum Clinical Trials UnitUM1AI154463 · NIAID · AURUM INSTITUTE NPC · PI Gavin John Churchyard · 2021 to 2026
$8.1M
Natural Resistance to Mycobacterium Tuberculosis InfectionU01AI115642 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI BOOM, W. HENRY, MAYANJA-KIZZA, HARRIET · 2015 to 2019
$3.5M
Epigenetic & Post-Translational Mechanisms of Macrophage Resistance to Mycobacterium tuberculosis During HIV Co-InfectionR33AI138272 · NIAID · UNIVERSITY OF WASHINGTON · PI BOOM, W. HENRY, HAWN, THOMAS R · 2020 to 2022
$3.4M
Macrophages and Resistance to Mycobacterium Tuberculosis Infection in HumansK08AI143926 · NIAID · UNIVERSITY OF WASHINGTON · PI SIMMONS, JASON · 2019 to 2023
$951k
Pulmonary Innate Immunity & Resistance to Mycobacterium Tuberculosis InfectionK24AI137310 · NIAID · UNIVERSITY OF WASHINGTON · PI HAWN, THOMAS R · 2018 to 2022
$892k
Medical Research Council MR/R010161/1NIAID NIH HHS K08 AI143926NIAID NIH HHS K24 AI137310NIAID NIH HHS N01 AI070022NIAID NIH HHS R01 AI124348NIAID NIH HHS R33 AI138272NIAID NIH HHS T32 AI007044NIAID NIH HHS U01 AI115642NIAID NIH HHS UM1 AI154463
6 · The paper itself

Abstract

After extensive exposure to Mycobacterium tuberculosis (Mtb), most individuals acquire latent Mtb infection (LTBI) defined by a positive tuberculin skin test (TST) or interferon-γ release assay (IGRA). To identify mechanisms of resistance to Mtb infection, we compared transcriptional profiles from highly exposed contacts who resist TST/IGRA conversion (resisters, RSTRs) and controls with LTBI using RNAseq. Gene sets related to carbon metabolism and free fatty acid (FFA) transcriptional responses enriched across 2 independent cohorts suggesting RSTR and LTBI monocytes have distinct activation states. We compared intracellular Mtb replication in macrophages treated with FFAs and found that palmitic acid (PA), but not oleic acid (OA), enhanced Mtb intracellular growth. This PA activity correlated with its inhibition of proinflammatory cytokines in Mtb-infected cells. Mtb growth restriction in PA-treated macrophages was restored by activation of AMP kinase (AMPK), a central host metabolic regulator known to be inhibited by PA. Finally, we genotyped AMPK variants and found 7 SNPs in PRKAG2, which encodes the AMPK-γ subunit, that strongly associated with RSTR status. Taken together, RSTR and LTBI phenotypes are distinguished by FFA transcriptional programs and by genetic variation in a central metabolic regulator, which suggests immunometabolic pathways regulate TST/IGRA conversion.

Indexed as

AMP-Activated Protein KinasesInterferon-gamma Release TestsLatent TuberculosisPolymorphism, Single NucleotideTranscription, GeneticTuberculin TestAdultHumansMaleMiddle AgedMonocytesMycobacterium tuberculosisU937 CellsAMP-Activated Protein KinasesPRKAG2 protein, humanFatty acid oxidationImmunologyInfectious diseaseInnate immunityTuberculosis

Identifiers

PMID34111032
PMCPMC8279582
OpenAlexW3170711239

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.