Evidence map›Paper›PMID 22295065›Full record

ArticlePloS one2012

TLR2/MyD88/NF-κB pathway, reactive oxygen species, potassium efflux activates NLRP3/ASC inflammasome during respiratory syncytial virus infection.

Jesus Segovia, Ahmed Sabbah, Victoria Mgbemena, Su-Yu Tsai, Te-Hung Chang, Michael T Berton, Ian R Morris, Irving C Allen, Jenny P-Y Ting, Santanu Bose

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 156 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
156citing papers in PubMed, 1 pooled it
11.0field-weighted citation impact, top 1% 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

156 citing papers in PubMed, 1 synthesis or guideline pooled it, 238 citations in OpenAlex.

  1. Pooled it
  2. Inflammasomes in respiratory diseases: from disease pathogenesis to drug development and use of multi-omics.European respiratory review : an official journal of the European Respiratory Society · 2026
    Review
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  5. [Epidemiology, Mechanisms, and Clinical Challenges of Respiratory Syncytial Virus Co-infections in Children].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2026
    Review
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96 more citing papers are in PubMed but not listed here.

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

10 authors at 2 institutions in 1 country.

Jesus SegoviaDepartment of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
Ahmed Sabbah
Victoria Mgbemena
Su-Yu Tsai
Te-Hung Chang
Michael T Berton
Ian R Morris
Irving C Allen
Jenny P-Y Ting
Santanu Bose
The University of Texas Health Science Center at San Antonio · USUNC Lineberger Comprehensive Cancer Center

Funding

Yessinia autotransporters (Yaps): Structure, function, and host responseU54AI057157 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SEMPOWSKI, GREGORY D · 2003 to 2013
$91.4M
Institutional Research Training GrantT32DE014318 · NIDCR · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Kenneth M Hargreaves · 2002 to 2026
$12.1M
P2X7 and the Inflammasome Pathways in Lung InflammationU19AI077437 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI PEDEN, DAVID B. · 2008 to 2013
$9.2M
Tularemia: Pathogenesis and Host ResponseP01AI057986 · NIAID · UNIVERSITY OF TEXAS SAN ANTONIO · PI KLOSE, KARL E · 2005 to 2009
$6.1M
Molecular and cellular mechanism regulating innate immunity and inflammation during pattern recognition receptor activation and respiratory virus infectionR01AI083387 · NIAID · WASHINGTON STATE UNIVERSITY · PI BOSE, SANTANU · 2010 to 2021
$3.1M
MOLECULAR MECHANISMS OF MICROBIAL PATHOGENICITYT32AI007271 · NIAID · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI ZHONG, GUANGMING · 1985 to 2013
$1.0M
NIAID NIH HHS AI057986NIAID NIH HHS AI083387NIAID NIH HHS P01 AI057986NIAID NIH HHS R01 AI083387NIAID NIH HHS T32 AI007271NIAID NIH HHS T32AI007271NIAID NIH HHS U19 AI077437NIAID NIH HHS U54 AI057157NIDCR NIH HHS DE14318NIDCR NIH HHS T32 DE014318
6 · The paper itself

Abstract

Human respiratory syncytial virus (RSV) constitute highly pathogenic virus that cause severe respiratory diseases in newborn, children, elderly and immuno-compromised individuals. Airway inflammation is a critical regulator of disease outcome in RSV infected hosts. Although "controlled" inflammation is required for virus clearance, aberrant and exaggerated inflammation during RSV infection results in development of inflammatory diseases like pneumonia and bronchiolitis. Interleukin-1β (IL-1β) plays an important role in inflammation by orchestrating the pro-inflammatory response. IL-1β is synthesized as an immature pro-IL-1β form. It is cleaved by activated caspase-1 to yield mature IL-1β that is secreted extracellularly. Activation of caspase-1 is mediated by a multi-protein complex known as the inflammasome. Although RSV infection results in IL-1β release, the mechanism is unknown. Here in, we have characterized the mechanism of IL-1β secretion following RSV infection. Our study revealed that NLRP3/ASC inflammasome activation is crucial for IL-1β production during RSV infection. Further studies illustrated that prior to inflammasome formation; the "first signal" constitutes activation of toll-like receptor-2 (TLR2)/MyD88/NF-κB pathway. TLR2/MyD88/NF-κB signaling is required for pro-IL-1β and NLRP3 gene expression during RSV infection. Following expression of these genes, two "second signals" are essential for triggering inflammasome activation. Intracellular reactive oxygen species (ROS) and potassium (K(+)) efflux due to stimulation of ATP-sensitive ion channel promote inflammasome activation following RSV infection. Thus, our studies have underscored the requirement of TLR2/MyD88/NF-κB pathway (first signal) and ROS/potassium efflux (second signal) for NLRP3/ASC inflammasome formation, leading to caspase-1 activation and subsequent IL-1β release during RSV infection.

Indexed as

Signal TransductionAnimalsCARD Signaling Adaptor ProteinsCarrier ProteinsCaspase 1Cell LineCytoskeletal ProteinsEnzyme ActivationGene Expression RegulationHumansInflammasomesInterleukin-1betaIntracellular SpaceKATP ChannelsMiceMyeloid Differentiation Factor 88CARD Signaling Adaptor ProteinsCarrier ProteinsCaspase 1Cytoskeletal ProteinsInflammasomesInterleukin-1betaKATP ChannelsMyeloid Differentiation Factor 88NF-kappa BNLR Family, Pyrin Domain-Containing 3 ProteinNLRP3 protein, humanPotassiumProtein PrecursorsPYCARD protein, humanReactive Oxygen SpeciesTLR2 protein, humanToll-Like Receptor 2

Identifiers

PMID22295065
PMCPMC3266238
OpenAlexW2034679941

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.