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Record W4387168380 · doi:10.7554/elife.87392

The chemorepellent, SLIT2, bolsters innate immunity against Staphylococcus aureus

2023· article· en· W4387168380 on OpenAlexafffund
Vikrant K. Bhosle, Chunxiang Sun, Sajedabanu Patel, Tse Wing Winnie Ho, Johannes Westman, Dustin A. Ammendolia, Fatemeh Mirshafiei Langari, Noah Fine, Nicole Toepfner, Zhubing Li, Manraj Sharma, Judah Glogauer, Mariana Capurro, Nicola L. Jones, Jason T. Maynes, Warren L. Lee, Michael Glogauer, Sergio Grinstein, Lisa A. Robinson

Bibliographic record

VenueeLife · 2023
Typearticle
Languageen
FieldImmunology and Microbiology
TopicNeutrophil, Myeloperoxidase and Oxidative Mechanisms
Canadian institutionsUniversity Health NetworkUniversity of TorontoSickKids FoundationPrincess Margaret Cancer CentreHospital for Sick Children
FundersNatural Sciences and Engineering Research Council of CanadaSvenska LäkaresällskapetStiftelsen Blanceflor Boncompagni Ludovisi, född BildtHospital for Sick ChildrenGovernment of OntarioCanada Research ChairsTechnische Universität DresdenCanada Foundation for InnovationCanadian Institutes of Health ResearchSick Kids Foundation
KeywordsStaphylococcus aureusInnate immune systemDegranulationChemotaxisNADPH oxidaseMicrobiologyImmunologyNeutrophil extracellular trapsBiologyp38 mitogen-activated protein kinasesAntimicrobial peptidesCell biologyInflammationImmune systemChemistryReactive oxygen speciesKinaseProtein kinase AAntimicrobialBacteriaReceptorBiochemistry

Abstract

fetched live from OpenAlex

Neutrophils are essential for host defense against Staphylococcus aureus ( S. aureus ). The neuro-repellent, SLIT2, potently inhibits neutrophil chemotaxis, and might, therefore, be expected to impair antibacterial responses. We report here that, unexpectedly, neutrophils exposed to the N-terminal SLIT2 (N-SLIT2) fragment kill extracellular S. aureus more efficiently. N-SLIT2 amplifies reactive oxygen species production in response to the bacteria by activating p38 mitogen-activated protein kinase that in turn phosphorylates NCF1, an essential subunit of the NADPH oxidase complex. N-SLIT2 also enhances the exocytosis of neutrophil secondary granules. In a murine model of S. aureus skin and soft tissue infection (SSTI), local SLIT2 levels fall initially but increase subsequently, peaking at 3 days after infection. Of note, the neutralization of endogenous SLIT2 worsens SSTI. Temporal fluctuations in local SLIT2 levels may promote neutrophil recruitment and retention at the infection site and hasten bacterial clearance by augmenting neutrophil oxidative burst and degranulation. Collectively, these actions of SLIT2 coordinate innate immune responses to limit susceptibility to S. aureus .

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 integrity0.0000.000
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 head0.017
GPT teacher head0.247
Teacher spread0.229 · 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

Citations11
Published2023
Admission routes2
Has abstractyes

Explore more

Same venueeLifeSame topicNeutrophil, Myeloperoxidase and Oxidative MechanismsFrench-language works237,207