Evidence map›Paper›PMID 40939292›Full record

ArticleEBioMedicine2025

TIM-3 ameliorates host responses to Salmonella infection by controlling iron driven CD4

Christa Pfeifhofer-Obermair, Natascha Brigo, Chiara Volani, Piotr Tymoszuk, Egon Demetz, Sabine Engl, Günter Weiss

Abstract read
In one paragraph

Article in EBioMedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Article
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

7 authors.

Christa Pfeifhofer-ObermairDepartment of Internal Medicine II, Medical University of Innsbruck, Anichstr. 35, Innsbruck 6020, Austria. Electronic address: christa.pfeifhofer@i-med.ac.at.
Natascha BrigoDepartment of Internal Medicine II, Medical University of Innsbruck, Anichstr. 35, Innsbruck 6020, Austria. Electronic address: natascha.brigo@i-med.ac.at.
Chiara VolaniDepartment of Internal Medicine II, Medical University of Innsbruck, Anichstr. 35, Innsbruck 6020, Austria. Electronic address: chiara.volani@i-med.ac.at.
Piotr TymoszukDepartment of Internal Medicine II, Medical University of Innsbruck, Anichstr. 35, Innsbruck 6020, Austria. Electronic address: piotr.s.tymoszuk@gmail.com.
Egon DemetzDepartment of Internal Medicine II, Medical University of Innsbruck, Anichstr. 35, Innsbruck 6020, Austria. Electronic address: egon.demetz@i-med.ac.at.
Sabine EnglDepartment of Internal Medicine II, Medical University of Innsbruck, Anichstr. 35, Innsbruck 6020, Austria. Electronic address: sabine.engl@i-med.ac.at.
Günter WeissDepartment of Internal Medicine II, Medical University of Innsbruck, Anichstr. 35, Innsbruck 6020, Austria; Christian Doppler Laboratory for Iron Metabolism and Anemia Research, Medical University of Innsbruck, Anichstr. 35, Innsbruck 6020, Austria. Electronic address: guenter.weiss@i-med.ac.at.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIron loading increases infection risk in being a nutrient for invading siderophilic bacteria and by modulating immune functions including the expression of the immune checkpoint regulator T-cell immunoglobulin-and-mucin-containing-domain-3 (TIM-3). TIM-3 affects specific immune cell functions including T-helper cell differentiation but also T cell dysfunction, and immune exhaustion. Given the prevalence of iron overload specifically in patients at higher risk for infection such as those suffering from hemo-oncological diseases, we investigated TIM-3's role in immune control of bacterial sepsis.

methodsA sepsis model was employed in wildtype and Tim3

findingsDietary iron supplementation reduced mouse survival, which was further exaggerated by TIM-3 deletion. This indicates that TIM-3 dependent immune regulation was essential for effective host defence against Salmonella. TIM-3 deletion increased the production of immune-deactivating interleukin (IL) -10 as a result of impaired interleukin-12 receptor (IL-12R)-dependent CD4

interpretationOur study uncovers TIM-3 as a crucial regulator of T cell driven immune control of bacterial infection and identifies the underlying treatable pathways, which is of major importance to better combat infection related mortality in subjects with iron overload syndromes.

fundingChristian-Doppler-Society, FWF (I-3321, W-1253).

Indexed as

CD4-Positive T-LymphocytesCell DifferentiationHepatitis A Virus Cellular Receptor 2Host-Pathogen InteractionsInterleukin-10IronSalmonella InfectionsAnimalsCation Transport ProteinsDisease Models, AnimalLymphocyte ActivationMiceMice, KnockoutNatural Resistance-associated Macrophage Protein 1Salmonella typhimuriumSepsisCation Transport ProteinsHavcr2 protein, mouseHepatitis A Virus Cellular Receptor 2Interleukin-10IronNatural Resistance-associated Macrophage Protein 1CD4 T cellsIFNgammaIL-10Intracellular bacteriaIronTIM-3

Identifiers

PMID40939292
PMCPMC12571576

What Socratic holds

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LicenceCC BY
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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 Socratic graph.