Evidence map›Paper›PMID 19265483›Full record

ArticleThe Journal of infectious diseases2009

HIV-1 Tat protein suppresses cholangiocyte toll-like receptor 4 expression and defense against Cryptosporidium parvum.

Steven P O'Hara, Aaron J Small, Gabriella B Gajdos, Andrew D Badley, Xian-Ming Chen, Nicholas F Larusso

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of infectious diseases, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.5field-weighted citation impact, top 12% 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

22 citing papers in PubMed, 34 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
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  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Advances in cholangiocyte immunobiology.American journal of physiology. Gastrointestinal and liver physiology · 2012
    Review
  15. Article
  16. Article
  17. Cryptosporidiosis-an overview.Journal of biomedical research · 2012
    Article
  18. Challenges in understanding the immunopathogenesis of Cryptosporidium infections in humans.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2011
    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

6 authors at 4 institutions in 1 country.

Steven P O'HaraMiles and Shirley Fiterman Center for Digestive Diseases, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Aaron J Small
Gabriella B Gajdos
Andrew D Badley
Xian-Ming Chen
Nicholas F Larusso
Center for Digestive and Liver Diseases · USCHI Health Creighton University Medical Center - Bergan Mercy · USCornell University · USMayo Clinic · US

Funding

Pathophysiology of Biliary DiseaseR01DK057993 · NIDDK · MAYO CLINIC ROCHESTER · PI LARUSSO, NICHOLAS F., O'HARA, STEVEN P · 2001 to 2025
$7.1M
MicroRNAs in Epithelial Innate Immunity to C. parvumR01AI071321 · NIAID · MAYO CLINIC ROCHESTER · PI CHEN, XIAN-MING · 2006 to 2010
$1.3M
Localized Water Influx During Cryptosporidium InvasionK01DK076922 · NIDDK · MAYO CLINIC ROCHESTER · PI O'HARA, STEVEN P · 2007 to 2009
$383k
NIAID NIH HHS R01 AI071321NIDDK NIH HHS DK57993NIDDK NIH HHS DK76922NIDDK NIH HHS K01 DK076922NIDDK NIH HHS R01 DK057993PHS HHS A1062261PHS HHS A2071321
6 · The paper itself

Abstract

Biliary cryptosporidiosis is associated with acquired immunodeficiency syndrome (AIDS) cholangiopathy and occurs almost exclusively in adult patients with AIDS. Infection of biliary epithelial cells (cholangiocytes) with Cryptosporidium parvum induces Toll-like receptor (TLR) 4 expression and stimulates a TLR-dependent response against infection. Here, we tested whether human immunodeficiency virus type 1 (HIV-1) Tat affects TLR expression and, hence, anti-C. parvum defense responses. Using an in vitro model of human biliary cryptosporidiosis, we found that recombinant Tat protein increased TLR4 mRNA expression in both uninfected and C. parvum-infected cholangiocytes. Conversely, Tat decreased TLR4 protein levels and suppressed C. parvum-induced TLR4 protein expression. Using actinomycin to inhibit transcription, we found that Tat increased the half-life of TLR4 mRNA from approximately 25 to 60 min, and RNA gel-shift assays demonstrated direct binding of Tat to TLR4 mRNA. In vitro transcription/translation studies suggested that Tat does not affect transcription but does decrease TLR4 translation. Importantly, more parasites were found in Tat-treated cells than in control cells 48 h after infection. These findings suggest that Tat inhibits cholangiocyte TLR4 protein expression through translational inhibition. These events appear to diminish the ability of cholangiocytes to initiate an innate immune response to C. parvum. We suggest that these findings may contribute to the unusual susceptibility of HIV-infected individuals to biliary cryptosporidiosis.

Indexed as

AnimalsBile DuctsCell Line, TransformedCryptosporidium parvumDose-Response Relationship, DrugGene Expression RegulationHumansRecombinant ProteinsRNA, Messengertat Gene Products, Human Immunodeficiency VirusToll-Like Receptor 4Recombinant ProteinsRNA, Messengertat Gene Products, Human Immunodeficiency VirusTLR4 protein, humanToll-Like Receptor 4

Identifiers

PMID19265483
PMCPMC2716168
OpenAlexW2110058830

What OpenQuestion holds

Textmetadata
LicenceTDM
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.