Evidence map›Paper›PMID 40435995›Full record

ArticleJournal of innate immunity2025

TLR2 or TLR4 Stimulation Induces Transmembrane TNF-Driven Priming in Macrophages Which Results in Improved Clearance of a Subsequent Staphylococcus aureus Infection.

Abby M Luu, Alexis A Hatton, Jasper Gattiker, Kelly M Shepardson, Monica N Hall, Evelyn Benson, Diane Bimczok, Agnieszka Rynda-Apple

Abstract read
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In one paragraph

Article in Journal of innate immunity, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

8 authors.

Abby M LuuDepartment of Microbiology and Cell Biology, Montana State University, Bozeman, Montana, USA, abbym.luu@gmail.com.
Alexis A HattonDepartment of Microbiology and Cell Biology, Montana State University, Bozeman, Montana, USA.
Jasper GattikerDepartment of Microbiology and Cell Biology, Montana State University, Bozeman, Montana, USA.
Kelly M ShepardsonDepartment of Molecular Cell Biology, University of California, Merced, California, USA.
Monica N HallDepartment of Microbiology and Cell Biology, Montana State University, Bozeman, Montana, USA.
Evelyn BensonDepartment of Microbiology and Cell Biology, Montana State University, Bozeman, Montana, USA.
Diane BimczokDepartment of Microbiology and Cell Biology, Montana State University, Bozeman, Montana, USA.
Agnieszka Rynda-AppleDepartment of Microbiology and Cell Biology, Montana State University, Bozeman, Montana, USA.

Funding

NRSA Training CoreTL1TR002318 · NCATS · UNIVERSITY OF WASHINGTON · PI Megan Moore · 2017 to 2026
$8.4M
Defining receptor-ligand interactions in gastric epithelial immunosurveillanceR21AI171903 · NIAID · MONTANA STATE UNIVERSITY - BOZEMAN · PI BIMCZOK, DIANE · 2022 to 2023
$412k
NCATS NIH HHS TL1 TR002318NIAID NIH HHS R21 AI171903
6 · The paper itself

Abstract

introductionToll-like receptor (TLR) engagement on macrophages can improve responsiveness to infection. TNF is upregulated following TLR2 or TLR4 stimulation. We sought to determine whether and how the two bioactive forms of TNF, soluble (sTNF) and transmembrane (tmTNF), may be contributing to macrophage priming, which improved responsiveness to subsequent Staphylococcus aureus infection.

methodsRNA sequencing and cytokine quantification assays identified differentially upregulated cytokines in response to TLR2 stimulation. Immortalized and primary bone marrow-derived macrophages (BMDMs) coupled with receptor blocking and cytokine supplementation were used to investigate whether/how prior TLR-primed macrophages improved S. aureus clearance.

resultsTLR2 or TLR4 stimulated TNF-/- BMDMs failed to efficiently clear a subsequent S. aureus infection compared to TLR-stimulated wild-type (WT) BMDMs. Depletion of sTNF from TLR-stimulated WT BMDMs retained their improved S. aureus clearance. Exogenous sTNF supplementation to TNF-/- BMDMs did not rescue improved S. aureus clearance. Cell density assays showed cell-to-cell contact was important for TLR-induced improvement of S. aureus clearance. Conversely, blocking TNFR2 reduced BMDM clearance of S. aureus, despite TLR2 stimulation.

conclusionsOur results demonstrated that TNF produced in response to TLR stimulated BMDMs was required for improved clearance of a subsequent S. aureus infection. We found that sTNF did not contribute to this priming, which suggested that tmTNF may be critical for BMDM priming which leads to improved S. aureus clearance.

Indexed as

MacrophagesStaphylococcal InfectionsStaphylococcus aureusToll-Like Receptor 2Toll-Like Receptor 4Tumor Necrosis Factor-alphaAnimalsCells, CulturedMacrophage ActivationMiceMice, Inbred C57BLMice, KnockoutTlr2 protein, mouseTlr4 protein, mouseTnf protein, mouseToll-Like Receptor 2Toll-Like Receptor 4Tumor Necrosis Factor-alphaBacteriaMacrophageStaphylococcus aureusToll-like receptorTransmembrane TNFTumor necrosis factor

Identifiers

PMID40435995
PMCPMC12187112

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LicenceCC BY-NC
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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.