Evidence map›Paper›PMID 40747802›Full record

ArticleThe Journal of infectious diseases2025

Elevated Spleen Tyrosine Kinase in Low-Density Neutrophils During Bacterial Sepsis in a Nonhuman Primate Model.

Heather L Teague, Seth Warner, Andrew P Platt, Sydney Stein, Marcos J Ramos-Benitez, Sabrina Ramelli, Shelly Curran, Izabella Lach, Kiana Allen, Heritage Adetola and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of infectious diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Association of CD16Journal of inflammation research · 2026
    Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Heather L TeagueCritical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
Seth WarnerCritical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
Andrew P PlattCritical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.ORCID 0000-0001-8481-114X
Sydney SteinCritical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
Marcos J Ramos-BenitezCritical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.ORCID 0000-0001-9445-3294
Sabrina RamelliCritical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
Shelly CurranCritical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.ORCID 0009-0005-2379-627X
Izabella LachCritical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
Kiana AllenCritical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.ORCID 0009-0009-1182-5749
Heritage AdetolaCritical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
Trevor StantliffCritical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.ORCID 0000-0003-2621-3111
Raquel Santana da CruzCritical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
Mahnaz MinaiBasic Science Department, Microbiology, Ponce Health Sciences University, Ponce, Puerto Rico, USA.
Heather KendallComparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Kevin M VannellaCritical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
Derron A AlvesComparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.ORCID 0009-0003-5993-182X
Richard HerbertComparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Daniel S ChertowCritical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
Jeffrey R StrichCritical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.

Funding

CLC NIH HHSNational Heart Lung and Blood InstituteNIH HHS
6 · The paper itself

Abstract

backgroundSepsis is a leading cause of death worldwide. Identifying novel host-directed therapeutic targets may improve sepsis outcomes.

methodsSix nonhuman primates were infected with Klebsiella pneumoniae to induce septic shock and provided supportive care for up to 72 hours. Flow cytometry was used to characterize whole-blood neutrophils (WBNs) and low-density neutrophils (LDNs) at time 0 (T0), T6, T24, and T48 hours postinfection, and postmortem examination (ie, necropsy). Dimensional reduction with clustering via FlowSOM and traditional gating strategies were used to compare WBNs to LDNs and delineate spleen tyrosine kinase (SYK) expression across neutrophils subsets. We measured soluble biomarkers of end-organ dysfunction and neutrophil activation, and quantified SYK and myeloperoxidase in tissue.

resultsAt T6, we identified populations of active immature WBNs and a population of LDNs not detected at baseline. At T24, neutrophil heterogeneity increased across WBNs and LDNs with differential expression of myeloperoxidase (MPO). Compared to WBNs, LDNs were more activated with increased MPO expression. At T6, SYK expression surged in WBNs and LDNs and SYK+ WBNs and LDNs expressed higher levels of MPO and lactoferrin compared to SYK- neutrophils. Circulating levels of SYK+ LDNs significantly correlated with serum creatinine levels, indicative of acute kidney injury; prolonged prothrombin time and decreased fibrinogen, indicative of consumptive coagulopathy; and SYK expression in tissues.

conclusionsBacterial sepsis leads to heterogenous populations of circulating neutrophils, including LDNs. Elevated SYK expression in WBNs and LDNs correlates with end-organ dysfunction, highlighting SYK as a potential therapeutic target in bacterial sepsis.

Indexed as

Klebsiella InfectionsNeutrophilsSepsisSyk KinaseAnimalsBiomarkersDisease Models, AnimalFemaleKlebsiella pneumoniaeMacaca mulattaMalePeroxidaseBiomarkersPeroxidaseSyk Kinaselow-density neutrophilssepsisspleen tyrosine kinase

Identifiers

PMID40747802
PMCPMC12718019

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.