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dc.contributor.authorO'NEILL, LUKE ANTHONY JOHNen
dc.contributor.authorKENNY, ELAINEen
dc.date.accessioned2011-09-22T14:59:51Z
dc.date.available2011-09-22T14:59:51Z
dc.date.issued2011en
dc.date.submitted2011en
dc.identifier.citationNathalie Court, Stephanie Rose, Marie-Laure Bourigault, Sophie Front, Olivier R. Martin, Jennifer K. Dowling, Elaine F. Kenny, Luke O'Neill, Francois Erard, Valerie F. J. Quesniaux, Mycobacterial PIMs Inhibit Host Inflammatory Responses through CD14-Dependent and CD14-Independent Mechanisms, PLoS ONE, 6, 9, e24631, 2011en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/59607
dc.descriptionPUBLISHEDen
dc.description.abstractMycobacteria develop strategies to evade the host immune system. Among them, mycobacterial LAM or PIMs inhibit the expression of pro-inflammatory cytokines by activated macrophages. Here, using synthetic PIM analogues, we analyzed the mode of action of PIM anti-inflammatory effects. Synthetic PIM1 isomer and PIM2 mimetic potently inhibit TNF and IL-12 p40 expression induced by TLR2 or TLR4 pathways, but not by TLR9, in murine macrophages. We show inhibition of LPS binding to TLR4/MD2/CD14 expressing HEK cells by PIM1 and PIM2 analogues. More specifically, the binding of LPS to CD14 was inhibited by PIM1 and PIM2 analogues. CD14 was dispensable for PIM1 and PIM2 analogues functional inhibition of TLR2 agonists induced TNF, as shown in CD14-deficient macrophages. The use of rough-LPS, that stimulates TLR4 pathway independently of CD14, allowed to discriminate between CD14-dependent and CD14-independent anti-inflammatory effects of PIMs on LPS-induced macrophage responses. PIM1 and PIM2 analogues inhibited LPS-induced TNF release by a CD14-dependent pathway, while IL-12 p40 inhibition was CD14-independent, suggesting that PIMs have multifold inhibitory effects on the TLR4 signalling pathway.en
dc.language.isoenen
dc.relation.ispartofseriesPLoS ONEen
dc.relation.ispartofseries6en
dc.relation.ispartofseries9, e24631en
dc.rightsYen
dc.subjectImmunologyen
dc.subjectInfectionen
dc.subjectMycobacteriaen
dc.subjectPIMen
dc.titleMycobacterial PIMs Inhibit Host Inflammatory Responses through CD14-Dependent and CD14-Independent Mechanismsen
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/laoneillen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/kennye6en
dc.identifier.rssinternalid75037en
dc.identifier.rssurihttp://dx.doi.org/10.1371/journal.pone.0024631en


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