Evidence map›Paper›PMID 37616312›Full record

ArticlePLoS genetics2023

Neutrophil extracellular trap formation and gene programs distinguish TST/IGRA sensitization outcomes among Mycobacterium tuberculosis exposed persons living with HIV.

Elouise E Kroon, Wilian Correa-Macedo, Rachel Evans, Allison Seeger, Lize Engelbrecht, Jurgen A Kriel, Ben Loos, Naomi Okugbeni, Marianna Orlova, Pauline Cassart and 7 more

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
1.2field-weighted citation impact, top 20% 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

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. 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

17 authors at 5 institutions in 4 countries.

Elouise E KroonDSI-NRF Centre of Excellence for Biomedical Tuberculosis Research; South African Medical Research Council Centre for Tuberculosis Research; Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.ORCID 0000-0002-8551-3301
Wilian Correa-MacedoProgram in Infectious Diseases and Immunity in Global Health, The Research Institute of the McGill University Health Centre, Montréal, Canada.
Rachel EvansInfectious Diseases and Immune Defence Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.ORCID 0009-0004-7956-5481
Allison SeegerWellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine and Department of Medicine, University of Cape Town, Observatory, South Africa.ORCID 0000-0002-5332-3722
Lize EngelbrechtCentral Analytical Facilities, Microscopy Unit, Stellenbosch University, Cape Town, South Africa.ORCID 0000-0002-4518-7011
Jurgen A KrielCentral Analytical Facilities, Microscopy Unit, Stellenbosch University, Cape Town, South Africa.
Ben LoosDepartment of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa.ORCID 0000-0002-5517-373X
Naomi OkugbeniDSI-NRF Centre of Excellence for Biomedical Tuberculosis Research; South African Medical Research Council Centre for Tuberculosis Research; Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.ORCID 0000-0003-3915-6152
Marianna OrlovaProgram in Infectious Diseases and Immunity in Global Health, The Research Institute of the McGill University Health Centre, Montréal, Canada.ORCID 0000-0002-8108-938X
Pauline CassartProgram in Infectious Diseases and Immunity in Global Health, The Research Institute of the McGill University Health Centre, Montréal, Canada.
Craig J KinnearDSI-NRF Centre of Excellence for Biomedical Tuberculosis Research; South African Medical Research Council Centre for Tuberculosis Research; Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Gerard C TrompDSI-NRF Centre of Excellence for Biomedical Tuberculosis Research; South African Medical Research Council Centre for Tuberculosis Research; Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.ORCID 0000-0002-7761-0806
Marlo MöllerDSI-NRF Centre of Excellence for Biomedical Tuberculosis Research; South African Medical Research Council Centre for Tuberculosis Research; Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.ORCID 0000-0002-0805-6741
Robert J WilkinsonWellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine and Department of Medicine, University of Cape Town, Observatory, South Africa.
Anna K CoussensInfectious Diseases and Immune Defence Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.ORCID 0000-0002-7086-2621
Erwin SchurrProgram in Infectious Diseases and Immunity in Global Health, The Research Institute of the McGill University Health Centre, Montréal, Canada.ORCID 0000-0002-2640-536X
Eileen G HoalDSI-NRF Centre of Excellence for Biomedical Tuberculosis Research; South African Medical Research Council Centre for Tuberculosis Research; Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.ORCID 0000-0002-6444-5688
South African Medical Research Council · ZAMcGill University Health Centre · CAStellenbosch University · ZAUniversity of Cape Town · ZAThe University of Melbourne · AU

Funding

Human genetics of TB resistance in HIV-infected personsR01AI124349 · NIAID · MCGILL UNIVERSITY HEALTH CTR RES INST · PI SCHURR, ERWIN · 2016 to 2020
$8.0M
NIAID NIH HHS R01 AI124349
6 · The paper itself

Abstract

Persons living with HIV (PLWH) have an increased risk for tuberculosis (TB). After prolonged and repeated exposure, some PLWH never develop TB and show no evidence of immune sensitization to Mycobacterium tuberculosis (Mtb) as defined by persistently negative tuberculin skin tests (TST) and interferon gamma release assays (IGRA). This group has been identified and defined as HIV+ persistently TB, tuberculin and IGRA negative (HITTIN). To investigate potential innate mechanisms unique to individuals with the HITTIN phenotype we compared their neutrophil Mtb infection response to that of PLWH, with no TB history, but who test persistently IGRA positive, and tuberculin positive (HIT). Neutrophil samples from 17 HITTIN (PMNHITTIN) and 11 HIT (PMNHIT) were isolated and infected with Mtb H37Rv for 1h and 6h. RNA was extracted and used for RNAseq analysis. Since there was no significant differential transcriptional response at 1h between infected PMNHITTIN and PMNHIT, we focused on the 6h timepoint. When compared to uninfected PMN, PMNHITTIN displayed 3106 significantly upregulated and 3548 significantly downregulated differentially expressed genes (DEGs) (absolute cutoff of a log2FC of 0.2, FDR < 0.05) whereas PMNHIT demonstrated 3816 significantly upregulated and 3794 significantly downregulated DEGs following 6h Mtb infection. Contrasting the log2FC 6h infection response to Mtb from PMNHITTIN against PMNHIT, 2285 genes showed significant differential response between the two groups. Overall PMNHITTIN had a lower fold change response to Mtb infection compared to PMNHIT. According to pathway enrichment, Apoptosis and NETosis were differentially regulated between HITTIN and HIT PMN responses after 6h Mtb infection. To corroborate the blunted NETosis transcriptional response measured among HITTIN, fluorescence microscopy revealed relatively lower neutrophil extracellular trap formation and cell loss in PMNHITTIN compared to PMNHIT, showing that PMNHITTIN have a distinct response to Mtb.

Indexed as

Extracellular TrapsHIV InfectionsMycobacterium tuberculosisHumansInterferon-gamma Release TestsTuberculinTuberculin

Identifiers

PMID37616312
PMCPMC10470897
OpenAlexW4386127118

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.