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Record W4414373989 · doi:10.1101/2025.09.17.676560

Bacterial suppression of intestinal fungi via activation of human gut γδ T-cells

2025· preprint· en· W4414373989 on OpenAlexaff
Liya Mathew, Sean Carlson, Michael P. Savage, Claire Pardieu, Megan B. O’Brien, Ellie Crawley, Paul Harrow, Ann-Kristin Kaune, Edward Devlin, Emily Priest, Marilena Crescente, Kimberly Martinod, James Boot, Marco Gasparetto, Klaartje Kok, James O. Lindsay, Jonathan P. Richardson, Julian R. Naglik, Andrew J. Stagg, Matthias Eberl, Siu Kwan Sze, Carol A. Munro, Neil E. McCarthy

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldMedicine
TopicClostridium difficile and Clostridium perfringens research
Canadian institutionsBrock University
FundersWellcome Trust
KeywordsExtracellularImmunityPopulationMacrophageImmune systemBacteriaFungusGut flora

Abstract

fetched live from OpenAlex

Abstract Gut symbionts condition mucosal immunity to resist infection by enteropathogens, but the specific microbes and mechanisms involved differ significantly between host species. In higher primates, bacterial metabolite HMB-PP is sensed by a specialized population of Vγ9Vδ2+T-cells, which we now report can potently suppress growth of endogenous fungi in human intestinal organ cultures. In healthy intestine, HMB-PP-stimulated Vδ2+T-cells restricted outgrowth of keystone fungus Candida albicans via a mechanism that required IL-22. In contrast, Crohn’s disease (CD) patients with reduced Vδ2+T-cell numbers displayed outgrowth of C. albicans strains that readily formed toxin-producing filaments, triggered neutrophil extracellular traps, and induced macrophage IL-1β release ex vivo . Genomic and proteomic analysis of the Candida isolates suggested increased tissue adhesion of CD-derived strains, which rapidly invaded the gut barrier in an ‘intestine-on-a-chip’ model. These data reveal that bacterial activation of Vδ2+T-cells suppresses fungal pathobionts in human gut via an IL-22-dependent mechanism that is dysregulated in CD.

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: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.004
Threshold uncertainty score0.013

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)0.0040.001

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 head0.023
GPT teacher head0.278
Teacher spread0.255 · 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 designBench or experimental
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

Citations0
Published2025
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicClostridium difficile and Clostridium perfringens research→French-language works237,207→