Evidence map›Paper›PMID 41790885›Full record

ArticleScience advances2026

Toll-like receptor signaling outcome is determined by the stoichiometry of the endogenous TRIFosome.

Martin C Moncrieffe, Prasanna Suresh, Joe Boyle, Yuhao Cui, Bharti Nawalpuri, Brett Verstak, Yu P Zhang, Ziwei Zhang, Marcus Taylor, Edward H Egelman and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. 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

13 authors.

Martin C MoncrieffeDepartment of Biochemistry, University of Cambridge, Cambridge, UK.ORCID 0000-0002-9074-6281
Prasanna SureshYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK.ORCID 0009-0001-5298-5994
Joe BoyleDepartment of Veterinary Medicine, University of Cambridge, Cambridge, UK.ORCID 0000-0002-4173-7805
Yuhao CuiYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK.ORCID 0009-0007-5761-8222
Bharti NawalpuriDepartment of Medicine, University of Cambridge, Cambridge, UK.ORCID 0000-0002-9218-0234
Brett VerstakDepartment of Biochemistry, University of Cambridge, Cambridge, UK.
Yu P ZhangYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK.
Ziwei ZhangYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK.
Marcus TaylorMax Planck Institute for Infection Biology, Berlin, Germany.ORCID 0000-0002-0904-2122
Edward H EgelmanDepartment of Biochemistry and Molecular Genetics, University of Charlottesville, Charlottesville, VA, USA.ORCID 0000-0003-4844-5212
Nicholas GayDepartment of Biochemistry, University of Cambridge, Cambridge, UK.
David KlenermanYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK.ORCID 0000-0001-7116-6954
Clare BryantDepartment of Veterinary Medicine, University of Cambridge, Cambridge, UK.ORCID 0000-0002-2924-0038

Funding

Cryo-EM of Helical Protein and Nucleoprotein Polymers at Near Atomic ResolutionR35GM122510 · NIGMS · UNIVERSITY OF VIRGINIA · PI EDWARD H. EGELMAN · 2017 to 2026
$7.3M
NIGMS NIH HHS R35 GM122510
6 · The paper itself

Abstract

Toll-like receptors (TLRs) drive innate immunity via assembly of macromolecular signal transduction platforms [supramolecular organizing centers (SMOCs)] coordinated by adaptor proteins such as Toll/interleukin-1 receptor (IL-1R) domain-containing adaptor-inducing interferon-β (TRIF), but whether oligomeric TRIFosomes form is unknown. Here, using cryo-electron microscopy and biophysical characterization of full-length TRIF in vitro, we show that it forms filamentous oligomers, which associate with the TRIF signaling partners receptor interacting protein 1 (RIP1) and RIP3 kinases, suggesting that oligomeric TRIFosomes could form. Endogenous TRIF, however, is predominantly monomeric in the absence of ligand, only forming TRIFosome oligomers in macrophages after stimulation of TLR4 or TLR3 when large, macromolecular signaling complexes form. TRIFosomes are fully formed 45 min after TLR3 or 60 min after TLR4 stimulation, commensurate with activation of nuclear factor κB in these cells. TLR3/4 activation triggers rapid interferon signaling prior to TRIFosome formation through monomeric TRIF, unexpectedly suggesting that a macromolecular platform of TRIF is not required to drive this signaling pathway. Collectively, these data show TRIFosome macromolecular platform formation and, unexpectedly, that TLR signaling can be SMOC-independent in addition to being SMOC-dependent.

Indexed as

Adaptor Proteins, Vesicular TransportSignal TransductionToll-Like ReceptorsAnimalsCryoelectron MicroscopyHumansInnate Immunity RecognitionMacrophagesMiceAdaptor Proteins, Vesicular TransportTicam1 protein, mouseToll-Like Receptors

Identifiers

PMID41790885
PMCPMC12965317

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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.