MétaCan
Menu
← Back to cohort
Record W4391385268 · doi:10.21203/rs.3.rs-3889020/v1

Mycobacterium tuberculosis resisters despite HIV exhibit activated T cells and macrophages in their pulmonary alveoli

2024· preprint· en· W4391385268 on OpenAlexafffund
Erwin Schurr, Monica Dallmann-Sauer, Vinicius M. Fava, Stephanus T. Malherbe, Candice McDonald, Marianna Orlova, Elouise E. Kroon, Aurélie Cobat, Stéphanie Boisson‐Dupuis, Eileen G. Hoal, Laurent Abel, Marlo Möller, Jean‐Laurent Casanova, Gerhard Walzl, Nelita du Plessis

Bibliographic record

VenueResearch Square · 2024
Typepreprint
Languageen
FieldMedicine
TopicTuberculosis Research and Epidemiology
Canadian institutionsMcGill University
FundersFaculty of Medicine and Health, University of SydneyNational Institute of Allergy and Infectious DiseasesMedical Research CouncilNational Institutes of HealthSt. Giles FoundationUniversiteit StellenboschAgence Nationale de Recherches sur le Sida et les Hépatites ViralesCHIST-ERAAgence Nationale de la RechercheSouth African Medical Research CouncilCanadian Institutes of Health ResearchAlliance de recherche numérique du CanadaMcGill University Health CentreMcGill UniversityInstitut des maladies génétiques Imagine
KeywordsMycobacterium tuberculosisHuman immunodeficiency virus (HIV)Pulmonary tuberculosisMicrobiologyTuberculosisVirologyImmunologyBiologyMedicinePathology

Abstract

fetched live from OpenAlex

Abstract To understand natural resistance to Mycobacterium tuberculosis (Mtb) infection, we studied people living with HIV (PLWH) in an area of high Mtb transmission. Given that alveolar leukocytes may contribute to this resistance, we performed single cell RNA-sequencing of bronchoalveolar lavage cells, unstimulated or ex vivo stimulated with Mtb. We obtained high quality cells for 7 participants who were TST & IGRA positive (called LTBI) and 6 who were persistently TST & IGRA negative (called resisters). Alveolar macrophages (AM) from resisters displayed more of an M1 phenotype relative to LTBI AM at baseline. Alveolar lymphocytosis (10%-60%) was exhibited by 5/6 resisters, resulting in higher numbers of CD4+ and CD8+ IFNG-expressing cells at baseline and upon Mtb challenge than LTBI samples. Mycobactericidal granulysin was expressed almost exclusively by a cluster of CD8+ T cells that co-expressed granzyme B, perforin and NK cell receptors. For resisters, these poly-cytotoxic T cells over-represented activating NK cell receptors and were present at 15-fold higher numbers in alveoli compared to LTBI. Altogether, our results showed that alveolar lymphocytosis, with increased numbers of alveolar IFNG-expressing cells and CD8+ poly-cytotoxic T cells, as well as activated AM were strongly associated with protection from persistent Mtb infection in PLWH.

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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.007

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)0.0020.000

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 head0.048
GPT teacher head0.371
Teacher spread0.323 · 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

Citations3
Published2024
Admission routes2
Has abstractyes

Explore more

Same venueResearch Square→Same topicTuberculosis Research and Epidemiology→French-language works237,207→