TLR2/MyD88/NF-kappa B Pathway, Reactive Oxygen Species, Potassium Efflux Activates NLRP3/ASC Inflammasome during Respiratory Syncytial Virus Infection

Simple item page
dc.contributor.advisorHuman 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-1b (IL-1b) plays an important role in inflammation by orchestrating the pro-inflammatory response. IL-1b is synthesized as an immature pro-IL-1b form. It is cleaved by activated caspase-1 to yield mature IL-1b 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-1b release, the mechanism is unknown. Here in, we have characterized the mechanism of IL-1b secretion following RSV infection. Our study revealed that NLRP3/ASC inflammasome activation is crucial for IL-1b 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-kB pathway. TLR2/MyD88/NF-kB signaling is required for pro-IL-1b 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-kB pathway (first signal) and ROS/potassium efflux (second signal) for NLRP3/ASC inflammasome formation, leading to caspase-1 activation and subsequent IL-1b release during RSV infection.en
dc.contributor.authorSegovia, Jesusen
dc.contributor.authorSabbah, Ahmeden
dc.contributor.authorMgbemena, Victoriaen
dc.contributor.authorTsai, Su-Yuen
dc.contributor.authorChang, Te-Hungen
dc.contributor.authorBerton, Michael T.en
dc.contributor.authorMorris, Ian R.en
dc.contributor.authorAllen, Irving C.en
dc.contributor.authorTing, Jenny P.-Y.en
dc.contributor.authorBose, Santanuen
dc.date.accessioned2017-01-10T00:49:46Zen
dc.date.available2017-01-10T00:49:46Zen
dc.date.issued2012-01-25en
dc.description.versionPublished versionen
dc.format.extent? - ? (15) page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0029695en
dc.identifier.issn1932-6203en
dc.identifier.issue1en
dc.identifier.urihttp://hdl.handle.net/10919/74045en
dc.identifier.volume7en
dc.language.isoenen
dc.publisherPLOSen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000301640600010&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectinnate antiviral responseen
dc.subjectnucleotide-binding domainen
dc.subjectanthrax lethal toxinen
dc.subjectleucine-rich repeaten
dc.subjecttoll-like receptorsen
dc.subjectcutting edgeen
dc.subjectcaspase-1 activationen
dc.subjectnalp3 inflammasomeen
dc.subjectviral-infectionen
dc.subjectgene-expressionen
dc.titleTLR2/MyD88/NF-kappa B Pathway, Reactive Oxygen Species, Potassium Efflux Activates NLRP3/ASC Inflammasome during Respiratory Syncytial Virus Infectionen
dc.title.serialPLOS ONEen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/Veterinary Medicineen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Biomedical Sciences and Pathobiologyen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/CVM T&R Facultyen

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
TLR2/MyD88/NF-κB pathway, reactive oxygen species, potassium efflux activates NLRP3/ASC inflammasome during respiratory syncytial virus infection.pdf
Size:
626.23 KB
Format:
Adobe Portable Document Format
Description:
Publisher's Version
Download
License bundle
Now showing 1 - 1 of 1
Name:
VTUL_Distribution_License_2016_05_09.pdf
Size:
18.09 KB
Format:
Adobe Portable Document Format
Description:
Download

Collections

All Faculty Deposits
Scholarly Works, Biomedical Sciences and Pathobiology