Evidence map›Paper›PMID 34342534›Full record

ArticlemSystems2021

Species-Specific Endotoxin Stimulus Determines Toll-Like Receptor 4- and Caspase 11-Mediated Pathway Activation Characteristics.

Orna Ernst, Mohd M Khan, Benjamin L Oyler, Sung Hwan Yoon, Jing Sun, Fang-Yu Lin, Nathan P Manes, Alexander D MacKerell, Iain D C Fraser, Robert K Ernst and 2 more

Open access · goldAbstract read
In one paragraph

Article in mSystems, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

16 citing papers in PubMed, 23 citations in OpenAlex.

  1. Review
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  10. Novel microbiotaFrontiers in microbiology · 2024
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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

12 authors at 2 institutions in 1 country.

Orna Ernst *Signaling Systems Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Mohd M Khan *Functional Cellular Networks Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Benjamin L OylerSchool of Medicine, University of Maryland, Baltimore, Maryland, USA.
Sung Hwan YoonFunctional Cellular Networks Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Jing SunSignaling Systems Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Fang-Yu LinComputer-Aided Drug Design Center, Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland, USA.
Nathan P ManesFunctional Cellular Networks Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Alexander D MacKerellComputer-Aided Drug Design Center, Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland, USA.
Iain D C FraserSignaling Systems Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Robert K ErnstDepartment of Microbial Pathogenesis, School of Dentistry, University of Maryland, Baltimore, Maryland, USA.
David R GoodlettDepartment of Microbial Pathogenesis, School of Dentistry, University of Maryland, Baltimore, Maryland, USA.
Aleksandra Nita-LazarFunctional Cellular Networks Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
National Institutes of Health · USUniversity of Maryland, Baltimore · US

Funding

RNAi Screening in Hematopoietic CellsZIAAI001106 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI FRASER, IAIN · 2009 to 2025
$12.4M
Analysis of Innate Immune Signaling NetworksZIAAI001107 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI FRASER, IAIN · 2009 to 2025
$11.9M
Protein Modifications Involved in Cell SignalingZIAAI001084 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI NITA-LAZAR, ALEKSANDRA · 2009 to 2025
$11.4M
Protection Against Gram-Negative Sepsis Conferred by Lipid A-Based Structural VariantsR01AI123820 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI ERNST, ROBERT K, GOODLETT, DAVID ROBINSON · 2016 to 2019
$1.5M
American Association of Pharmaceutical Scientists (AAPS)Division of Intramural Research, National Institute of Allergy and Infectious Diseases (DIR, NIAID)Genome Canada (Génome Canada) 264PROHHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) 1R01AI123820-01International Research Agenda's Program for the Foundation of Polish Science MAB/2017/03NIAID NIH HHS R01 AI123820
6 · The paper itself

Abstract

The innate immune system is the body's first line of defense against pathogens and its protection against infectious diseases. On the surface of host myeloid cells, Toll-like receptor 4 (TLR4) senses lipopolysaccharide (LPS), the major outer membrane component of Gram-negative bacteria. Intracellularly, LPS is recognized by caspase 11 through the noncanonical inflammasome to induce pyroptosis-an inflammatory form of lytic cell death. While TLR4-mediated signaling perturbations result in secretion of cytokines and chemokines that help clear infection and facilitate adaptive immunity, caspase 11-mediated pyroptosis leads to the release of damage-associated molecular patterns and inflammatory mediators. Although the core signaling events and many associated proteins in the TLR4 signaling pathway are known, the complex signaling events and protein networks within the noncanonical inflammasome pathway remain obscure. Moreover, there is mounting evidence for pathogen-specific innate immune tuning. We characterized the major LPS structures from two different pathogens, modeled their binding to the surface receptors, systematically examined macrophage inflammatory responses to these LPS molecules, and surveyed the temporal differences in global protein secretion resulting from TLR4 and caspase 11 activation in macrophages using mass spectrometry (MS)-based quantitative proteomics. This integrated strategy, spanning functional activity assays, top-down structural elucidation of endotoxins, and secretome analysis of stimulated macrophages, allowed us to identify crucial differences in TLR4- and caspase 11-mediated protein secretion in response to two Gram-negative bacterial endotoxins.

Indexed as

caspase 11caspasescytokineshost-pathogen interactionshost responseinfectioninflammasomeinnate immunitylipopolysaccharidemacrophagesproteomicssecretomeSILCSsite identification by ligand competitive saturationToll-like receptors

Identifiers

PMID34342534
PMCPMC8407122
OpenAlexW3192590880

What OpenQuestion holds

Textmetadata
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.