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dc.contributor.authorLavelle, Edwarden
dc.contributor.authorMoran, Barryen
dc.contributor.authorMc Loughlin, Rachelen
dc.date.accessioned2011-06-02T14:56:07Z
dc.date.available2011-06-02T14:56:07Z
dc.date.issued2010en
dc.date.submitted2010en
dc.identifier.citationMcNeela EA, Burke A, Neill DR, Baxter C, Fernandes VE, Ferreira D, Smeaton S, El-Rachkidy R, McLoughlin RM, Mori A, Moran B, Fitzgerald KA, Tschopp J, Pétrilli V, Andrew PW, Kadioglu A, Lavelle EC, Pneumolysin activates the NLRP3 inflammasome and promotes proinflammatory cytokines independently of TLR4., PLoS pathogens, 6, 11, 2010, e1001191en
dc.identifier.issn1553-7366en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/56345
dc.descriptionPUBLISHEDen
dc.description.abstractPneumolysin (PLY) is a key Streptococcus pneumoniae virulence factor and potential candidate for inclusion in pneumococcal subunit vaccines. Dendritic cells (DC) play a key role in the initiation and instruction of adaptive immunity, but the effects of PLY on DC have not been widely investigated. Endotoxin-free PLY enhanced costimulatory molecule expression on DC but did not induce cytokine secretion. These effects have functional significance as adoptive transfer of DC exposed to PLY and antigen resulted in stronger antigen-specific T cell proliferation than transfer of DC exposed to antigen alone. PLY synergized with TLR agonists to enhance secretion of the proinflammatory cytokines IL-12, IL-23, IL-6, IL-1?, IL-1? and TNF-? by DC and enhanced cytokines including IL-17A and IFN-? by splenocytes. PLY-induced DC maturation and cytokine secretion by DC and splenocytes was TLR4-independent. Both IL-17A and IFN-? are required for protective immunity to pneumococcal infection and intranasal infection of mice with PLY-deficient pneumococci induced significantly less IFN-? and IL-17A in the lungs compared to infection with wild-type bacteria. IL-1? plays a key role in promoting IL-17A and was previously shown to mediate protection against pneumococcal infection. The enhancement of IL-1? secretion by whole live S. pneumoniae and by PLY in DC required NLRP3, identifying PLY as a novel NLRP3 inflammasome activator. Furthermore, NLRP3 was required for protective immunity against respiratory infection with S. pneumoniae. These results add significantly to our understanding of the interactions between PLY and the immune system.en
dc.format.extente1001191en
dc.language.isoenen
dc.relation.ispartofseriesPLoS pathogensen
dc.relation.ispartofseries6en
dc.relation.ispartofseries11en
dc.rightsYen
dc.subjectImmunologyen
dc.subjectPneumolysinen
dc.subjectBiochemistryen
dc.titlePneumolysin activates the NLRP3 inflammasome and promotes proinflammatory cytokines independently of TLR4.en
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/lavelleeen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/mclougrmen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/moranbaen
dc.identifier.rssinternalid73509en
dc.identifier.doihttp://dx.doi.org/10.1371/journal.ppat.100119en
dc.subject.TCDThemeImmunology, Inflammation & Infectionen
dc.identifier.rssurihttp://dx.doi.org/10.1371/journal.ppat.1001191en
dc.identifier.orcid_id0000-0002-3167-1080en


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