Evidence map›Paper›PMID 15501764›Full record

ArticleInfection and immunity2004

The Type II heat-labile enterotoxins LT-IIa and LT-IIb and their respective B pentamers differentially induce and regulate cytokine production in human monocytic cells.

George Hajishengallis, Hesham Nawar, Richard I Tapping, Michael W Russell, Terry D Connell

Abstract read
In one paragraph

Article in Infection and immunity, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.7field-weighted citation impact, top 11% 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

30 citing papers in PubMed, 46 citations in OpenAlex.

  1. Article
  2. The diverse landscape of AB5-type toxins.Engineering microbiology · 2023
    Review
  3. Shiga Toxin, Stx2e, Influences the Activity of Porcine Lymphocytes In Vitro.International journal of molecular sciences · 2023
    Article
  4. RecombinantAntibiotics (Basel, Switzerland) · 2022
    Review
  5. The Role ofToxins · 2020
    Review
  6. Article
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  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
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  16. Article
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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

5 authors at 3 institutions in 1 country.

George HajishengallisLouisiana State University Health Sciences Center, Department of Microbiology, Immunology, and Parasitology, Center of Excellence in Oral and Craniofacial Biology, 1100 Florida Ave., Box 130, New Orleans 70119, USA. ghajis@lsuhsc.edu
Hesham Nawar
Richard I Tapping
Michael W Russell
Terry D Connell
University at Buffalo, State University of New York · USLouisiana State University Health Sciences Center New Orleans · USUniversity of Illinois Urbana-Champaign · US

Funding

P. gingivalis as a keystone pathogenR01DE015254 · NIDCR · UNIVERSITY OF PENNSYLVANIA · PI HAJISHENGALLIS, GEORGIOS · 2004 to 2018
$4.6M
TYPE II Enterotoxins as Mucosal ImmunomodulatorsR01DE013833 · NIDCR · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI CONNELL, TERRY D. · 2001 to 2010
$3.2M
ANTIGENS OF STREPTOCOCCUS MUTANS IN CARIES IMMUNITYR37DE006746 · NIDCR · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI RUSSELL, MICHAEL W · 1999 to 2008
$2.4M
Initiation of Toll-like Receptor SignalingR01AI052344 · NIAID · UNIVERSITY OF ILLINOIS URBANA-CHAMPAIGN · PI TAPPING, RICHARD IAN · 2005 to 2009
$1.4M
Type II enterotoxins as mucosal immunomodulatorsR56DE013833 · NIDCR · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI CONNELL, TERRY D. · 2011 to 2011
$317k
Initiation of Toll-like Receptor SignalingR21AI052344 · NIAID · UNIVERSITY OF ILLINOIS URBANA-CHAMPAIGN · PI TAPPING, RICHARD IAN · 2004 to 2004
$299k
PROTEIN ANTIGENS OF STREP MUTANS IN CARIES IMMUNITYR01DE006746 · NIDCR · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI RUSSELL, MICHAEL W · 1985 to 1998
–
NIAID NIH HHS AI052344NIAID NIH HHS R01 AI052344NIAID NIH HHS R21 AI052344NIDCR NIH HHS DE015254NIDCR NIH HHS DE06746NIDCR NIH HHS DE13833NIDCR NIH HHS R01 DE013833NIDCR NIH HHS R01 DE015254NIDCR NIH HHS R37 DE006746NIDCR NIH HHS R56 DE013833
6 · The paper itself

Abstract

The type II heat-labile enterotoxins, LT-IIa and LT-IIb, exhibit potent adjuvant properties. However, little is known about their immunomodulatory activities upon interaction with innate immune cells, unlike the widely studied type I enterotoxins that include cholera toxin (CT). We therefore investigated interactions of LT-IIa and LT-IIb with human monocytic THP-1 cells. We found that LT-II enterotoxins were inactive in stimulating cytokine release, whereas CT induced low levels of interleukin-1beta (IL-1beta) and IL-8. However, all three enterotoxins potently regulated cytokine induction in cells activated by bacterial lipopolysaccharide or fimbriae. Induction of proinflammatory (tumor necrosis factor alpha [TNF-alpha]) or chemotactic (IL-8) cytokines was downregulated, whereas induction of cytokines with anti-inflammatory (IL-10) or mucosal adjuvant properties (IL-1beta) was upregulated by the enterotoxins. These effects appeared to depend on their A subunits, because isolated B-pentameric subunits lacked regulatory activity. Enterotoxin-mediated inhibition of proinflammatory cytokine induction in activated cells was partially attributable to synergism for endogenous production of IL-10 and to an IL-10-independent inhibition of nuclear factor kappaB (NF-kappaB) activation. In sharp contrast to the holotoxins, the B pentamers (LT-IIaB and, to a greater extent, LT-IIbB) stimulated cytokine production, suggesting a link between the absence of the A subunit and increased proinflammatory properties. In this regard, the ability of LT-IIbB to activate NF-kappaB and induce TNF-alpha and IL-8 was antagonized by the LT-IIb holotoxin. These findings support distinct immunomodulatory roles for the LT-II holotoxins and their respective B pentamers. Moreover, the anti-inflammatory properties of the holotoxins may serve to suppress innate immunity and promote the survival of the pathogen.

Indexed as

Gene Expression RegulationBacterial ToxinsCell LineCholera ToxinCytokinesEnterotoxinsEscherichia coliEscherichia coli ProteinsHumansInflammationInterleukin-10LipopolysaccharidesMonocytesNF-kappa BBacterial ToxinsCholera ToxinCytokinesEnterotoxinsEscherichia coli Proteinsheat-labile enterotoxin, E coliInterleukin-10LipopolysaccharidesNF-kappa B

Identifiers

PMID15501764
PMCPMC523043
OpenAlexW2161061586

What OpenQuestion holds

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Registered trials

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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.