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Record W4366772878 · doi:10.1101/2023.04.19.537498

<sub> Altered neutrophil extracellular traps in response to <i>Mycobacterium tuberculosis</i> in persons living with HIV with no previous TB and negative TST and IGRA </sub>

2023· preprint· en· W4366772878 on OpenAlexaff
Elouise E. Kroon, Wilian Correa-Macedo, Roger G. Evans, A. Seeger, Louise Engelbrecht, JA Kriel, Ben Loos, Naomi Okugbeni, Marianna Orlova, Pauline Cassart, Craig Kinnear, GC Tromp, Marlo Möller, RJ Wilkinson, AK Coussens, Erwin Schurr, Eileen G. Hoal

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2023
Typepreprint
Languageen
FieldImmunology and Microbiology
TopicNeutrophil, Myeloperoxidase and Oxidative Mechanisms
Canadian institutionsMcGill UniversityMcGill University Health Centre
FundersUniversiteit Stellenbosch
KeywordsTuberculosisImmunologyMycobacterium tuberculosisMedicineDownregulation and upregulationImmune systemNeutrophil extracellular trapsTuberculinGeneBiologyInflammationPathology

Abstract

fetched live from OpenAlex

Abstract Persons living with HIV (PLWH) have an increased risk for tuberculosis (TB). After prolonged and repeated exposure, some PLWH never develop TB and test persistently negative in tests of immune sensitization tuberculin skin test (TST) and interferon gamma release assays (IGRA) for Mycobacterium tuberculosis ( Mtb) . 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 (PMN HITTIN ) and 11 HIT (PMN HIT ) were isolated and infected with Mtb H37Rv for 1h and 6h. RNA was extracted and used for RNAseq analysis. At 1h of Mtb infection, PMN HITTIN displayed 151 significantly upregulated and 40 significantly downregulated differentially expressed genes (DEGs) and PMN HIT 98 significantly upregulated and 11 significantly downregulated DEGs. At the 6h timepoint, PMN HITTIN displayed 3106 significantly upregulated and 3548 significantly downregulated DEGs while PMN HIT had 3816 significantly up- and 3794 significantly downregulated DEGs. There was no significant differential transcriptional response at 1h between infected PMN HITTIN and PMN HIT. However, when contrasting the log 2 FC 6h infection response to Mtb from PMN HITTIN against PMN HIT , 2285 genes showed significant differential response between the two groups. Apoptosis and NETosis were key pathways linked to the enrichment of genes in PMN HITTIN when contrasted to PMN HIT after 6h infection with Mtb . Fluorescence microscopy revealed relatively lower neutrophil extracellular trap formation and cell loss in PMN HITTIN compared to PMN HIT , showing that PMN HITTIN have a distinct response to Mtb .

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.010
GPT teacher head0.196
Teacher spread0.186 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations2
Published2023
Admission routes1
Has abstractyes

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