ArticleCell communication and signaling : CCS2026
Extracellular vesicles derived from Enterococcus faecalis: inflammatory activation does not require internalization.
Article in Cell communication and signaling : CCS, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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.
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.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEnterococcus faecalis is a common gut commensal Gram-positive bacterium that can act as an opportunistic pathogen and is frequently associated with severe infections community-acquired and nosocomial. Bacteria-derived extracellular vesicles (EVs) emerge as key mediators of host-bacteria communication with immunomodulatory roles and mechanistic participation in pathophysiological processes. However, the impact of E. faecalis-derived EVs (Ef-EVs) on host cells and their potential role in shaping host responses during infection remain unclear.
methodsEf-EVs from the E. faecalis DSM 20478 type strain and four independent clinical bloodstream isolates were isolated via ultracentrifugation and size exclusion chromatography. EVs were characterized by nanoparticle tracking analysis and cryogenic transmission electron microscopy. Immunomodulatory effects of Ef-EVs were studied in vitro on NF-κB/AP-1 reporter cells, primary human monocyte-derived macrophages, and human umbilical vein endothelial cells, and by transcriptomic analysis of macrophages isolated from in vivo EV-treated zebrafish larvae. EV-induced signaling mechanisms were studied using uptake inhibitors as well as bottom-up assembled bacterial EVs functionalized with synthetic bacterial ligands. EV-induced metabolic reprogramming in macrophages was investigated by RNA-Seq and live-cell metabolic analyses using the Seahorse XFe-96 Flux Analyzer.
resultsWe found that Ef-EVs can induce pro-inflammatory responses in host macrophages via Toll-like receptor 2 (TLR2) signaling, as demonstrated using TLR2 transgenic cell lines and a TLR2-blocking antibody. Using uptake inhibitors as well as bottom-up assembled bacterial EVs functionalized with synthetic bacterial ligands as a minimalistic approach to study mechanisms of EV signaling, we demonstrated that Ef-EVs target the plasma membrane TLR2 to induce inflammation in a process uncoupled from their internalization. Furthermore, we found that Ef-EVs induce metabolic reprogramming towards a pro-inflammatory, glycolytic phenotype.
conclusionOur findings reveal a mechanism by which Gram-positive bacterial EVs modulate immune signaling and metabolic pathways, advancing our understanding of host-pathogen communication.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.