Show simple item record

dc.contributor.authorBowie, Andrew
dc.contributor.authorMusilova, Jana
dc.contributor.authorMulcahy, Michelle E.
dc.contributor.authorKuijk, Marieke M.
dc.contributor.authorMcLoughlin, Rachel M.
dc.date.accessioned2020-01-15T13:03:58Z
dc.date.available2020-01-15T13:03:58Z
dc.date.issued2019en
dc.date.submitted2019en
dc.identifier.citationMusilova, J., Mulcahy, M.E., Kuijk, M.M., McLoughlin, R.M. & Bowie, A.G., Toll-like receptor 2-dependent endosomal signaling by Staphylococcus aureus in monocytes induces type i interferon and promotes intracellular survival, 2019, Journal of Biological Chemistry, 294, 45en
dc.identifier.otherY
dc.identifier.urihttp://hdl.handle.net/2262/91327
dc.identifier.urihttp://www.jbc.org/content/294/45/17031
dc.description.abstractPathogen activation of innate immune pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) stimulates cellular signaling pathways. This often leads to outcomes that contribute to pathogen clearance. Alternatively, activation of specific PRR pathways can aid pathogen survival. The human pathogen Staphylococcus aureus is a case in point, employing strategies to escape innate immune recognition and killing by the host. As for other bacteria, PRR-stimulated type I interferon (IFN-I) induction has been proposed as one such immune escape pathway that may favor S. aureus. Cell wall components of S. aureus elicit TLR2-dependent cellular responses, but the exact signaling pathways activated by S. aureus-TLR2 engagement and the consequences of their activation for the host and bacterium are not fully known. We previously showed that TLR2 activates both a cytoplasmic and an endosome-dependent signaling pathway, the latter leading to IFN-I production. Here, we demonstrate that S. aureus infection of human monocytes activates a TLR2-dependent endosomal signaling pathway, leading to IFN-I induction. We mapped the signaling components of this pathway and identified roles in IFN-I stimulation for the Toll-interleukin-1 receptor(TIR) adaptorMyd88 adaptor-like(Mal),TNF receptor-associated factor 6 (TRAF6), and IB kinase (IKK)-related kinases, but not for TRIF-related adaptor molecule (TRAM) and TRAF3. Importantly, monocyte TLR2-dependent endosomal signaling enabled immune escape for S. aureus, because this pathway, but not IFN-I per se, contributedto intracellular bacterial survival. These results reveal a TLR2-dependent mechanism in human monocytes whereby S. aureus manipulates innate immune signaling for its survival in cellsen
dc.format.extent17031-17042en
dc.language.isoenen
dc.relation.ispartofseriesJournal of Biological Chemistry;
dc.relation.ispartofseries294;
dc.relation.ispartofseries45;
dc.rightsYen
dc.subjectInnate immunityen
dc.subjectHost-pathogen interactionen
dc.subjectToll-like receptor (TLR)en
dc.subjectStaphylococcus aureus (S. aureus)en
dc.subjectMonocyteen
dc.subjectInterferonen
dc.subjectInfectious diseaseen
dc.subjectImmune evasionen
dc.subjectNonprofessional phagocyteen
dc.titleToll-like receptor 2-dependent endosomal signaling by Staphylococcus aureus in monocytes induces type i interferon and promotes intracellular survivalen
dc.typeJournal Articleen
dc.contributor.sponsorScience Foundation Irelanden
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/agbowie
dc.identifier.rssinternalid210057
dc.identifier.doihttp://dx.doi.org/10.1074/jbc.RA119.009302
dc.rights.ecaccessrightsopenAccess
dc.contributor.sponsorGrantNumber16/IA/4376en
dc.contributor.sponsorGrantNumber15/IA/3041en
dc.contributor.sponsorGrantNumber11/PI/1056en
dc.identifier.orcid_id0000-0001-5316-4373


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record