Evidence map›Paper›PMID 37306596›Full record

ArticleMicrobiology spectrum2023

Characterization of the Inflammatory Response Evoked by Bacterial Membrane Vesicles in Intestinal Cells Reveals an RIPK2-Dependent Activation by Enterotoxigenic Escherichia coli Vesicles.

Himadri B Thapa, Paul Kohl, Franz G Zingl, Dominik Fleischhacker, Heimo Wolinski, Thomas A Kufer, Stefan Schild

Open access · goldAbstract read
In one paragraph

Article in Microbiology spectrum, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
3.1field-weighted citation impact, top 8% of its field
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

14 citing papers in PubMed, 17 citations in OpenAlex.

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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

7 authors at 2 institutions in 2 countries.

Himadri B Thapa *Institute of Molecular Biosciences, University of Graz, Graz, Austria.ORCID 0000-0001-8965-6716
Paul Kohl *Institute of Molecular Biosciences, University of Graz, Graz, Austria.
Franz G ZinglInstitute of Molecular Biosciences, University of Graz, Graz, Austria.ORCID 0000-0003-0874-4234
Dominik FleischhackerInstitute of Molecular Biosciences, University of Graz, Graz, Austria.ORCID 0009-0009-0799-0709
Heimo WolinskiInstitute of Molecular Biosciences, University of Graz, Graz, Austria.
Thomas A KuferDepartment of Immunology, Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
Stefan SchildInstitute of Molecular Biosciences, University of Graz, Graz, Austria.ORCID 0000-0001-7842-0177
University of Graz · ATUniversity of Hohenheim · DE

Funding

Austrian Science Fund FWF DOC 50
6 · The paper itself

Abstract

Although the immunomodulatory potency of bacterial membrane vesicles (MVs) is widely acknowledged, their interactions with host cells and the underlying signaling pathways have not been well studied. Herein, we provide a comparative analysis of the proinflammatory cytokine profile secreted by human intestinal epithelial cells exposed to MVs derived from 32 gut bacteria. In general, outer membrane vesicles (OMVs) from Gram-negative bacteria induced a stronger proinflammatory response than MVs from Gram-positive bacteria. However, the quality and quantity of cytokine induction varied between MVs from different species, highlighting their unique immunomodulatory properties. OMVs from enterotoxigenic Escherichia coli (ETEC) were among those showing the strongest proinflammatory potency. In depth analyses revealed that the immunomodulatory activity of ETEC OMVs relies on a so far unprecedented two-step mechanism, including their internalization into host cells followed by intracellular recognition. First, OMVs are efficiently taken up by intestinal epithelial cells, which mainly depends on caveolin-mediated endocytosis as well as the presence of the outer membrane porins OmpA and OmpF on the MVs. Second, lipopolysaccharide (LPS) delivered by OMVs is intracellularly recognized by novel caspase- and RIPK2-dependent pathways. This recognition likely occurs via detection of the lipid A moiety as ETEC OMVs with underacylated LPS exhibited reduced proinflammatory potency but similar uptake dynamics compared to OMVs derived from wild-type (WT) ETEC. Intracellular recognition of ETEC OMVs in intestinal epithelial cells is pivotal for the proinflammatory response as inhibition of OMV uptake also abolished cytokine induction. The study signifies the importance of OMV internalization by host cells to exercise their immunomodulatory activities.

Indexed as

Enterotoxigenic Escherichia coliBacteriaBacterial Outer Membrane ProteinsCytokinesHumansIntestinesLipopolysaccharidesReceptor-Interacting Protein Serine-Threonine Kinase 2Bacterial Outer Membrane ProteinsCytokinesLipopolysaccharidesReceptor-Interacting Protein Serine-Threonine Kinase 2RIPK2 protein, humanbacterial membrane vesiclescaspasecytokinecytokinesETECHT-29IL-8inflammatory responseinterleukinsintestinal epithelial celllipopolysaccharideLPSOMVouter membrane vesiclesporinporinsRIPK2

Identifiers

PMID37306596
PMCPMC10433812
OpenAlexW4380291017

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.