Evidence map›Paper›PMID 34669717›Full record

ArticlePLoS pathogens2021

Comparative transcriptional profiling of the early host response to infection by typhoidal and non-typhoidal Salmonella serovars in human intestinal organoids.

Basel H Abuaita, Anna-Lisa E Lawrence, Ryan P Berger, David R Hill, Sha Huang, Veda K Yadagiri, Brooke Bons, Courtney Fields, Christiane E Wobus, Jason R Spence and 2 more

Open access · goldAbstract readComparative Study
In one paragraph

Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.7field-weighted citation impact, top 13% 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

20 citing papers in PubMed, 31 citations in OpenAlex.

  1. Review
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  8. Heterogeneity ofInfection and immunity · 2024
    Article
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  18. Cross-Talk Between the Intestinal Epithelium andFrontiers in microbiology · 2022
    Review
  19. Article
  20. 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

12 authors at 1 institution in 1 country.

Basel H AbuaitaDepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.ORCID 0000-0001-6492-2707
Anna-Lisa E LawrenceDepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
Ryan P BergerDepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.ORCID 0000-0002-0023-8129
David R HillDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
Sha HuangDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
Veda K YadagiriDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
Brooke BonsDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
Courtney FieldsDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.ORCID 0000-0002-8996-453X
Christiane E WobusDepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.ORCID 0000-0001-5286-0924
Jason R SpenceDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
Vincent B YoungDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.ORCID 0000-0003-3687-2364
Mary X O'RiordanDepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.ORCID 0000-0001-6014-4637
University of Michigan · US

Funding

Molecular Mechanisms of Microbial Pathogenesis Training ProgramT32AI007528 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CARRUTHERS, VERNON BRUCE · 1998 to 2024
$6.8M
Stem Cell Differentiation CoreU19AI116482 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WOBUS, CHRISTIANE · 2015 to 2019
$6.4M
NIAID NIH HHS T32 AI007528NIAID NIH HHS U19 AI116482
6 · The paper itself

Abstract

Salmonella enterica represents over 2500 serovars associated with a wide-ranging spectrum of disease; from self-limiting gastroenteritis to invasive infections caused by non-typhoidal serovars (NTS) and typhoidal serovars, respectively. Host factors strongly influence infection outcome as malnourished or immunocompromised individuals can develop invasive infections from NTS, however, comparative analyses of serovar-specific host responses have been constrained by reliance on limited model systems. Here we used human intestinal organoids (HIOs), a three-dimensional "gut-like" in vitro system derived from human embryonic stem cells, to elucidate similarities and differences in host responses to NTS and typhoidal serovars. HIOs discriminated between the two most prevalent NTS, Salmonella enterica serovar Typhimurium (STM) and Salmonella enterica serovar Enteritidis (SE), and typhoidal serovar Salmonella enterica serovar Typhi (ST) in epithelial cell invasion, replication and transcriptional responses. Pro-inflammatory signaling and cytokine output was reduced in ST-infected HIOs compared to NTS infections, consistent with early stages of NTS and typhoidal diseases. While we predicted that ST would induce a distinct transcriptional profile from the NTS strains, more nuanced expression profiles emerged. Notably, pathways involved in cell cycle, metabolism and mitochondrial functions were downregulated in STM-infected HIOs and upregulated in SE-infected HIOs. These results correlated with suppression of cellular proliferation and induction of host cell death in STM-infected HIOs and in contrast, elevated levels of reactive oxygen species production in SE-infected HIOs. Collectively, these results suggest that the HIO model is well suited to reveal host transcriptional programming specific to infection by individual Salmonella serovars, and that individual NTS may provoke unique host epithelial responses during intestinal stages of infection.

Indexed as

Gene Expression ProfilingHumansIntestinesOrganoidsSalmonella entericaSalmonella InfectionsSerogroupTranscriptome

Identifiers

PMID34669717
PMCPMC8570492
OpenAlexW3205052185

What OpenQuestion holds

Textmetadata
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.