Granuloma Formation and Host Defense in Chronic Mycobacterium tuberculosis Infection Requires PYCARD/ASC but Not NLRP3 or Caspase-1

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dc.contributor.authorTeKippe, Erin McElvaniaen
dc.contributor.authorAllen, Irving C.en
dc.contributor.authorHulseberg, Paul D.en
dc.contributor.authorSullivan, Jonathan T.en
dc.contributor.authorMcCann, Jessica R.en
dc.contributor.authorSandor, Matysen
dc.contributor.authorBraunstein, Miriamen
dc.contributor.authorTing, Jenny P.-Y.en
dc.date.accessioned2017-01-10T00:48:52Zen
dc.date.available2017-01-10T00:48:52Zen
dc.date.issued2010-08-20en
dc.description.abstractThe NLR gene family mediates host immunity to various acute pathogenic stimuli, but its role in chronic infection is not known. This paper addressed the role of NLRP3 (NALP3), its adaptor protein PYCARD (ASC), and caspase-1 during infection with Mycobacterium tuberculosis (Mtb). Mtb infection of macrophages in culture induced IL-1b secretion, and this requires the inflammasome components PYCARD, caspase-1, and NLRP3. However, in vivo Mtb aerosol infection of Nlrp32/2, Casp-12/2, and WT mice showed no differences in pulmonary IL-1b production, bacterial burden, or long-term survival. In contrast, a significant role was observed for Pycard in host protection during chronic Mtb infection, as shown by an abrupt decrease in survival of Pycard2/2 mice. Decreased survival of Pycard2/2 animals was associated with defective granuloma formation. These data demonstrate that PYCARD exerts a novel inflammasome-independent role during chronic Mtb infection by containing the bacteria in granulomas.en
dc.description.versionPublished versionen
dc.format.extent? - ? (10) page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0012320en
dc.identifier.issn1932-6203en
dc.identifier.issue8en
dc.identifier.urihttp://hdl.handle.net/10919/74043en
dc.identifier.volume5en
dc.language.isoenen
dc.publisherPLOSen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000281077000014&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.subjectpulmonary tuberculosisen
dc.subjectimmune-responseen
dc.subjectcell-deathen
dc.subjectinflammasome activationen
dc.subjectgene familyen
dc.subjectt-cellsen
dc.subjectmiceen
dc.subjectascen
dc.subjectproteinen
dc.subjectinterleukin-1-betaen
dc.titleGranuloma Formation and Host Defense in Chronic Mycobacterium tuberculosis Infection Requires PYCARD/ASC but Not NLRP3 or Caspase-1en
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

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