OSCR

TLR4 signaling drives tissue inflammation, Claudin-5 internalization, and vascular barrier breakdown in a mouse model of neonatal meningitis.

Overview

Authors: Philip V Seegren1,2, Amir Rattner1,2, Philip M Smallwood1,2, Yanshu Wang1,2, Jeremy Nathans1,2,3,4
ORCID iDs: Philip V Seegren, Amir Rattner, Jeremy Nathans
  1. Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, United States
  2. Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States
  3. Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States
  4. Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, United States
Institutions: Howard Hughes Medical Institute (United States); Johns Hopkins University (United States); Johns Hopkins Medicine (United States)
Journal: eLife, volume 15, article RP110458
Dates: published online 18 August 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.7554/elife.110458 · PMID 42611752 · PMCID PMC13485302 · OpenAlex W7128699089
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: genetics / omics (modality), human (organism), mouse (organism), other condition (population)
Methods: Statistics, Smoothing, state filtering, decompositions, Preprocessing, fMRI & imaging
Keywords: Mouse
MeSH: Claudin-5*, Inflammation*, Meningitis, Escherichia coli*, Signal Transduction*, Toll-Like Receptor 4*, Animals, Animals, Newborn, Capillary Permeability, Cell Line, Disease Models, Animal, Endothelial Cells, Escherichia coli, Mice, Mice, Knockout, NF-kappa B (* major topic)
Topic: Bacterial Infections and Vaccines (Microbiology, Immunology and Microbiology), according to OpenAlex
Funding: Howard Hughes Medical Institute
Citations: cited by 1 paper (Europe PMC); 91 references in the paper
Research resources: sgTrack-mCherry plasmid RRID:Addgene_114013, Lenti-Cas9-Blast plasmid RRID:Addgene_52962

Abstract

Neonatal bacterial meningitis is a leading cause of infant morbidity and mortality, yet the molecular and cellular basis of the leptomeningeal response to infection remains poorly defined. Here, we study a mouse model of neonatal Escherichia coli meningitis, combining conditional gene knockouts, leptomeningeal single-nucleus RNA sequencing, and endothelial cell culture to explore the role of Toll-like receptor 4 (TLR4) signaling in the host response to infection. Deletion of Tlr4 in non-myeloid cells dramatically reduced the inflammatory response in all leptomeningeal cell types and abrogated the infection-associated increase in vascular permeability. In a brain endothelial cell line (bEnd.3 cells), exposure to E. coli triggered NF-κB activation, selective internalization of Claudin-5, and increased monolayer permeability, responses that were eliminated by Tlr4 knockout. RNA-seq showed that TLR4 controls an NF-κB–driven transcriptional program that orchestrates the endothelial response to E. coli. These findings reveal multiple TLR4-dependent host responses to neonatal Gram-negative bacterial meningitis.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none, so it has no map.

Data

Datasets cited

Data availability

RNA sequence data were deposited in GEO (accession number GSE319556 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE319556)). All data generated or analyzed during this study are included in the manuscript, supporting files, and GEO submission.

The following dataset was generated:

Seegren PV, Rattner A, Smallwood PM, Wang Y, Nathans J. 2026. Endothelial TLR4 signaling drives tissue inflammation, Claudin-5 internalization, and vascular barrier breakdown in a mouse model of neonatal meningitis. NCBI Gene Expression Omnibus. GSE319556

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 2, 28 September 2026

  • Funding: added Howard Hughes Medical Institute

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 5 authors, 1 keyword, 15 MeSH terms, 85 references, 2 RRIDs.

Cite

This paper

Seegren, P. V., Rattner, A., Smallwood, P. M., Wang, Y., & Nathans, J. (2026). TLR4 signaling drives tissue inflammation, Claudin-5 internalization, and vascular barrier breakdown in a mouse model of neonatal meningitis. eLife, 15, RP110458. https://doi.org/10.7554/elife.110458

BibTeX

@article{seegren2026tlr4,
author = {Seegren, Philip V and Rattner, Amir and Smallwood, Philip M and Wang, Yanshu and Nathans, Jeremy},
title = {{TLR4 signaling drives tissue inflammation, Claudin-5 internalization, and vascular barrier breakdown in a mouse model of neonatal meningitis}},
journal = {eLife},
year = {2026},
month = aug,
volume = {15},
pages = {RP110458},
publisher = {eLife Sciences Publications, Ltd},
issn = {2050-084X},
doi = {10.7554/elife.110458},
url = {https://doi.org/10.7554/elife.110458},
pmid = {42611752},
pmcid = {PMC13485302}
}

RIS

TY - JOUR
AU - Seegren, Philip V
AU - Rattner, Amir
AU - Smallwood, Philip M
AU - Wang, Yanshu
AU - Nathans, Jeremy
TI - TLR4 signaling drives tissue inflammation, Claudin-5 internalization, and vascular barrier breakdown in a mouse model of neonatal meningitis
T2 - eLife
J2 - eLife
PY - 2026
DA - 2026/08/18
VL - 15
SP - RP110458
SN - 2050-084X
PB - eLife Sciences Publications, Ltd
DO - 10.7554/elife.110458
UR - https://doi.org/10.7554/elife.110458
LA - en
ER -

CSL-JSON

{
"id": "10.7554/elife.110458",
"type": "article-journal",
"title": "TLR4 signaling drives tissue inflammation, Claudin-5 internalization, and vascular barrier breakdown in a mouse model of neonatal meningitis",
"container-title": "eLife",
"author": [
{
"family": "Seegren",
"given": "Philip V"
},
{
"family": "Rattner",
"given": "Amir"
},
{
"family": "Smallwood",
"given": "Philip M"
},
{
"family": "Wang",
"given": "Yanshu"
},
{
"family": "Nathans",
"given": "Jeremy"
}
],
"container-title-short": "eLife",
"volume": "15",
"page": "RP110458",
"DOI": "10.7554/elife.110458",
"PMID": "42611752",
"PMCID": "PMC13485302",
"ISSN": "2050-084X",
"publisher": "eLife Sciences Publications, Ltd",
"URL": "https://doi.org/10.7554/elife.110458",
"language": "en",
"issued": {
"date-parts": [
[
2026,
8,
18
]
]
}
}

Similar papers

The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.

[1] doi:10.1080/21505594.2026.2670939
Integrated transcriptomic and proteomic analysis reveals inflammatory activation and blood-brain barrier disruption during meningitis-associated extraintestinal pathogenic <i>Escherichia coli</i> infection.
Journal: Virulence
In common: genetics / omics, other condition, mouse, 3 references
[2] doi:10.1186/s12974-026-03794-3
Single-cell omics and flow cytometry identify distinct immune states of dural and brain-infiltrating IL-17-producing γδ T cells after experimental stroke.
Journal: Journal of neuroinflammation
In common: genetics / omics, mouse, 4 references
[3] doi:10.1038/s41593-026-02358-1 [code]
Cerebral venous blood flow regulates intracerebral pressure and brain clearance via meningeal lymphatic vessels.
Journal: Nature neuroscience
In common: mouse, 3 references
[4] doi:10.1093/neuonc/noag080
Laser interstitial thermal therapy enhances bidirectional blood-brain barrier permeability in glioblastoma.
Journal: Neuro-oncology
In common: genetics / omics, other condition, mouse, 2 references
[5] doi:10.1210/endocr/bqag087
A single-nucleus multiomic study of preoptic area cells in prepubertal control vs prenatally androgenized female mice.
Journal: Endocrinology
In common: genetics / omics, mouse, 3 references
[6] doi:10.1080/21505594.2026.2721762
Identification of a mechanical signaling pathway activating type 1 fimbriae via a ZraSR two-component system in neonatal meningitis-associated <i>Escherichia coli</i>.
Journal: Virulence
In common: other condition, mouse, 2 references
[7] doi:10.1016/j.cell.2026.05.026 [code]
The critical role of the endogenous immune compartment after CAR T cell therapy in recurrent GBM.
Journal: Cell
In common: genetics / omics, other condition, 3 references
[8] doi:10.1016/j.isci.2026.115973
<i>Cryptococcus neoformans</i> invasion of the orbital compartment and periocular spaces following intracerebral infection in mice.
Journal: iScience
In common: other condition, mouse, 2 references
[9] doi:10.5409/wjcp.v15.i2.114986
Epidemiological trends and neurological outcomes of pediatric central nervous system infections in rural part of western India.
Journal: World journal of clinical pediatrics
In common: other condition, 2 references
[10] doi:10.1186/s12348-026-00638-2
Putative mechanisms of ocular inflammation in syphilis.
Journal: Journal of ophthalmic inflammation and infection
In common: other condition, 2 references

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Sign in with ORCID to claim this paper as one of its authors, correct its record or validate its tracing map: when the paper's metadata lists your ORCID iD, you are recognized at once. Maintainers of its code: sign in with GitHub, then claim the repository on your account page.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion, reproductions, activity

Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.

Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.