Evidence map›Paper›PMID 30849550›Full record

ArticleCellular and molecular gastroenterology and hepatology2019

Interferon-λ3 Promotes Epithelial Defense and Barrier Function Against Cryptosporidium parvum Infection.

Sylvia H Ferguson, Derek M Foster, Barbara Sherry, Scott T Magness, Dahlia M Nielsen, Jody L Gookin

Abstract read
In one paragraph

Article in Cellular and molecular gastroenterology and hepatology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing 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

39 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Mechanisms of Differential Signal Transduction by IFNLR1 Variants.bioRxiv : the preprint server for biology · 2025
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. IFN-λ3 is induced byInfection and immunity · 2024
    Article
  14. Review
  15. Review
  16. Analysis of intestinal epithelial cell responses tobioRxiv : the preprint server for biology · 2023
    Article
  17. Article
  18. Review
  19. Review
  20. Early immune and host cell responses toFrontiers in parasitology · 2023
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Sylvia H FergusonDepartment of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina; Comparative Medicine Institute, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina.
Derek M FosterComparative Medicine Institute, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina; Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina.
Barbara SherryComparative Medicine Institute, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina; Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina.
Scott T MagnessComparative Medicine Institute, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina; Department of Medicine, Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, North Carolina; Joint Department of Biomedical Engineering, University of North Carolina, Chapel Hill, and North Carolina State University, Raleigh, North Carolina; Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, and North Carolina State University, Raleigh, North Carolina.
Dahlia M NielsenDepartment of Biological Sciences, North Carolina State University, Raleigh, North Carolina; Bioinformatics Research Center, North Carolina State University, Raleigh, North Carolina.
Jody L GookinDepartment of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina; Comparative Medicine Institute, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina; Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina; Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, and North Carolina State University, Raleigh, North Carolina. Electronic address: jody_gookin@ncsu.edu.

Funding

Comparative Medicine and Translational Research Training ProgramT32OD011130 · OD · NORTH CAROLINA STATE UNIVERSITY RALEIGH · PI Lauren Virginia Schnabel · 2012 to 2026
$7.8M
NIH HHS T32 OD011130
6 · The paper itself

Abstract

BACKGROUND &

aimsThe epithelial response is critical for intestinal defense against Cryptosporidium, but is poorly understood. To uncover the host strategy for defense against Cryptosporidium, we examined the transcriptional response of intestinal epithelial cells (IECs) to C parvum in experimentally infected piglets by microarray. Up-regulated genes were dominated by targets of interferon (IFN) and IFN-λ3 was up-regulated significantly in infected piglet mucosa. Although IFN-λ has been described as a mediator of epithelial defense against viral pathogens, there is limited knowledge of any role against nonviral pathogens. Accordingly, the aim of the study was to determine the significance of IFN-λ3 to epithelial defense and barrier function during C parvum infection.

methodsThe significance of C parvum-induced IFN-λ3 expression was determined using an immunoneutralization approach in neonatal C57BL/6 mice. The ability of the intestinal epithelium to up-regulate IFN-λ2/3 expression in response to C parvum infection and the influence of IFN-λ2/3 on epithelial defense against C parvum invasion, intracellular development, and loss of barrier function was examined using polarized monolayers of a nontransformed porcine-derived small intestinal epithelial cell line (IPEC-J2). Specifically, changes in barrier function were quantified by measurement of transepithelial electrical resistance and transepithelial flux studies.

resultsImmunoneutralization of IFN-λ2/3 in C parvum-infected neonatal mice resulted in a significantly increased parasite burden, fecal shedding, and villus blunting with crypt hyperplasia during peak infection. In vitro, C parvum was sufficient to induce autonomous IFN-λ3 and interferon-stimulated gene 15 expression by IECs. Priming of IECs with recombinant human IFN-λ3 promoted cellular defense against C parvum infection and abrogated C parvum-induced loss of barrier function by decreasing paracellular permeability to sodium.

conclusionsThese studies identify IFN-λ3 as a key epithelial defense mechanism against C parvum infection.

Indexed as

Up-RegulationAnimalsCell LineCryptosporidiosisCryptosporidium parvumCytokinesDisease Models, AnimalGene Expression ProfilingInterferon LambdaInterleukinsIntestinal MucosaMiceMice, Inbred C57BLOligonucleotide Array Sequence AnalysisSwineCytokinesInterferon Lambdainterferon-lambda protein, mouseInterleukinsCryptosporidiosisCytokineEnterocyteProtozoa

Identifiers

PMID30849550
PMCPMC6510929

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.