Evidence map›Paper›PMID 38898166›Full record

ArticleNature chemical biology2024

3-Hydroxykynurenine targets kainate receptors to promote defense against infection.

Margarita Parada-Kusz, Anne E Clatworthy, Emily R Goering, Stephanie M Blackwood, Jack Y Shigeta, Eivgeni Mashin, Elizabeth J Salm, Catherine Choi, Senya Combs, Jenny S W Lee and 4 more

Abstract read
In one paragraph

Article in Nature chemical biology, 2024. 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. Review
  2. Article
  3. Channeling kynurenine.Nature chemical biology · 2024
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Margarita Parada-Kusz *Department of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital (MGH), Boston, MA, USA.
Anne E Clatworthy *Department of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital (MGH), Boston, MA, USA. clatwort@broadinstitute.org.ORCID http://orcid.org/0000-0002-5033-1014
Emily R GoeringDepartment of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital (MGH), Boston, MA, USA.ORCID http://orcid.org/0000-0002-0843-831X
Stephanie M BlackwoodDepartment of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital (MGH), Boston, MA, USA.ORCID http://orcid.org/0009-0008-7777-5011
Jack Y ShigetaDepartment of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital (MGH), Boston, MA, USA.ORCID http://orcid.org/0009-0008-9797-7542
Eivgeni MashinBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Elizabeth J SalmDepartment of Cellular and Molecular Physiology and Neuroscience, Yale School of Medicine, New Haven, CT, USA.
Catherine ChoiDepartment of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital (MGH), Boston, MA, USA.
Senya CombsDepartment of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital (MGH), Boston, MA, USA.
Jenny S W LeeDepartment of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital (MGH), Boston, MA, USA.
Carlos Rodriguez-OsorioDepartment of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital (MGH), Boston, MA, USA.ORCID http://orcid.org/0000-0002-4972-4611
Clary ClishBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-8259-9245
Susumu TomitaDepartment of Cellular and Molecular Physiology and Neuroscience, Yale School of Medicine, New Haven, CT, USA.
Deborah T HungDepartment of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital (MGH), Boston, MA, USA. hung@molbio.mgh.harvard.edu.ORCID http://orcid.org/0000-0003-4262-0673

Funding

Skill Development for Diverse Scientific Careers: A New Course Predoctoral Program in Cellular and Molecular BiologyT32GM007223 · NIGMS · YALE UNIVERSITY · PI BASERGA, SUSAN J · 1985 to 2019
$31.0M
Regulation of glutamate receptors by calcium-dependent protein kinasesR01MH077939 · NIMH · YALE UNIVERSITY · PI TOMITA, SUSUMU · 2008 to 2023
$5.2M
Regulation of glutamate receptors by calcium-dependent protein kinaseR56MH077939 · NIMH · YALE UNIVERSITY · PI TOMITA, SUSUMU · 2013 to 2014
$833k
NIGMS NIH HHS T32 GM007223NIMH NIH HHS R01 MH077939NIMH NIH HHS R56 MH077939
6 · The paper itself

Abstract

Bacterial infection involves a complex interaction between the pathogen and host where the outcome of infection is not solely determined by pathogen eradication. To identify small molecules that promote host survival by altering the host-pathogen dynamic, we conducted an in vivo chemical screen using zebrafish embryos and found that treatment with 3-hydroxykynurenine (3-HK) protects from lethal bacterial infection. 3-HK, a metabolite produced through host tryptophan metabolism, has no direct antibacterial activity but enhances host survival by restricting bacterial expansion in macrophages through a systemic mechanism that targets kainate-sensitive glutamate receptors. These findings reveal a new pathway by which tryptophan metabolism and kainate-sensitive glutamate receptors function and interact to modulate immunity, with important implications for the coordination between the immune and nervous systems in pathological conditions.

Indexed as

Kainic Acid ReceptorsKynurenineZebrafishAnimalsEmbryo, NonmammalianHost-Pathogen InteractionsMacrophagesMiceTryptophan3-hydroxykynurenineKainic Acid ReceptorsKynurenineTryptophan

Identifiers

PMID38898166
PMCPMC12204212

What OpenQuestion holds

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Registered trials

None linked

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.