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Record W3196009884 · doi:10.1038/s41467-021-24982-0

Listeria exploits IFITM3 to suppress antibacterial activity in phagocytes

2021· article· en· W3196009884 on OpenAlexafffund
Joel M. J. Tan, Monica E. Garner, James Regeimbal, Catherine J. Greene, Jorge David Rojas Márquez, Dustin A. Ammendolia, Adam R. R. McCluggage, Taoyingnan Li, Katherine J. Wu, Marija Cemma, Philip P. Ostrowski, Brian Raught, Michael Diamond, Sergio Grinstein, Robin M. Yates, Darren E. Higgins, John H. Brumell

Bibliographic record

VenueNature Communications · 2021
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmune Response and Inflammation
Canadian institutionsSickKids FoundationUniversity of TorontoUniversity Health NetworkUniversity of CalgaryPrincess Margaret Cancer CentreHospital for Sick Children
FundersOffice of Extramural Research, National Institutes of HealthNational Institute of Allergy and Infectious DiseasesNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health ResearchNational Institutes of HealthU.S. Department of Health and Human ServicesGovernment of CanadaHospital for Sick ChildrenOntario Innovation TrustScheme for Promotion of Academic and Research Collaboration
KeywordsPhagosomeListeria monocytogenesIntracellular parasiteMicrobiologyBiologyInterferonImmune systemListeriaCell biologyIntracellularVirulenceSignal transductionTransmembrane proteinImmunologyBacteriaGeneReceptor

Abstract

fetched live from OpenAlex

Abstract The type I interferon (IFN) signaling pathway has important functions in resistance to viral infection, with the downstream induction of interferon stimulated genes (ISG) protecting the host from virus entry, replication and spread. Listeria monocytogenes (Lm), a facultative intracellular foodborne pathogen, can exploit the type I IFN response as part of their pathogenic strategy, but the molecular mechanisms involved remain unclear. Here we show that type I IFN suppresses the antibacterial activity of phagocytes to promote systemic Lm infection. Mechanistically, type I IFN suppresses phagosome maturation and proteolysis of Lm virulence factors ActA and LLO, thereby promoting phagosome escape and cell-to-cell spread; the antiviral protein, IFN-induced transmembrane protein 3 (IFITM3), is required for this type I IFN-mediated alteration. Ifitm3−/− mice are resistant to systemic infection by Lm, displaying decreased bacterial spread in tissues, and increased immune cell recruitment and pro-inflammatory cytokine signaling. Together, our findings show how an antiviral mechanism in phagocytes can be exploited by bacterial pathogens, and implicate IFITM3 as a potential antimicrobial therapeutic target.

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 score0.001
Threshold uncertainty score0.004

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 integrity0.0000.001
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 head0.023
GPT teacher head0.307
Teacher spread0.284 · 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

Citations30
Published2021
Admission routes2
Has abstractyes

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