The TLR4 adaptor TRAM controls the phagocytosis of Gram-negative bacteria by interacting with the Rab11-family interacting protein 2

dc.contributor.authorSkjesol, Astrid
dc.contributor.authorYurchenko, Mariia
dc.contributor.authorBösl, Korbinian
dc.contributor.authorGravastrand, Caroline
dc.contributor.authorNilsen, Kaja Elisabeth
dc.contributor.authorGrøvdal, Lene Melsæther
dc.contributor.authorAgliano, Federica
dc.contributor.authorPatane, Francesco
dc.contributor.authorLentini, Germana
dc.contributor.authorKim, Hera
dc.contributor.authorTeti, Giuseppe
dc.contributor.authorKumar Sharma, Aditya
dc.contributor.authorKandasamy, Richard K.
dc.contributor.authorSporsheim, Bjørnar
dc.contributor.authorStarheim, Kristian K.
dc.contributor.authorGolenbock, Douglas T.
dc.contributor.authorStenmark, Harald
dc.contributor.authorMcCaffrey, Mary
dc.contributor.authorEspevik, Terje
dc.contributor.authorHusebye, Harald
dc.contributor.funderNorges Teknisk-Naturvitenskapelige Universiteten
dc.contributor.funderNorges Forskningsråden
dc.contributor.funderLiaison Committee for Education, Research and Innovation, Norwayen
dc.date.accessioned2019-11-19T11:59:27Z
dc.date.available2019-11-19T11:59:27Z
dc.date.issued2019-03-18
dc.description.abstractAuthor summary The Gram-negative bacteria E. coli is the most common cause of severe human pathological conditions like sepsis. Sepsis is a clinical syndrome defined by pathological changes due to systemic inflammation, resulting in paralysis of adaptive T-cell immunity with IFN-β as a critical factor. TLR4 is a key sensing receptor of lipopolysaccharide on Gram-negative bacteria. Inflammatory signalling by TLR4 is initiated by the use of alternative pair of TIR-adapters, MAL-MyD88 or TRAM-TRIF. MAL-MyD88 signaling occurs mainly from the plasma membrane giving pro-inflammatory cytokines like TNF, while TRAM-TRIF signaling occurs from vacuoles like endosomes and phagosomes to give type I interferons like IFN-β. It has previously been shown that TLR4 can control phagocytosis and phagosomal maturation through MAL-MyD88 in mice, however, these data have been disputed and published before the role of TRAM was defined in the induction of IFN-β. A role for TRAM or TRIF in phagocytosis has not previously been reported. Here we describe a novel mechanism where TRAM and its binding partner Rab11-FIP2 control phagocytosis of E. coli and regulate IRF3 dependent production of IFN-β. The significance of these results is that we define Rab11-FIP2 as a potential target for modulation of TLR4-dependent signalling in different pathological states.en
dc.description.sponsorship46082500; 80420223; 223255/F50; FRIMEDBIO program (275876); 50052400en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleide1007684en
dc.identifier.citationSkjesol, A., Yurchenko, M., Bösl, K., Gravastrand, C., Nilsen, K.E., Grøvdal, L.M., Agliano, F., Patane, F., Lentini, G., Kim, H. and Teti, G., 2019. The TLR4 adaptor TRAM controls the phagocytosis of Gram-negative bacteria by interacting with the Rab11-family interacting protein 2. PLoS pathogens, 15(3), (e1007684). DOI:10.1371/journal.ppat.1007684en
dc.identifier.doi10.1371/journal.ppat.1007684en
dc.identifier.eissn1553-7374
dc.identifier.endpage30en
dc.identifier.issn1553-7366
dc.identifier.issued3en
dc.identifier.journaltitlePLoS Pathogensen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/9067
dc.identifier.volume15en
dc.language.isoenen
dc.publisherPLoSen
dc.relation.urihttps://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007684
dc.rights© 2019 Skjesol et alen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectPhagocytosisen
dc.subjectToll-like receptor 4 (TLR4)en
dc.subjectRab11 family interacting protein 2 (FIP2)en
dc.titleThe TLR4 adaptor TRAM controls the phagocytosis of Gram-negative bacteria by interacting with the Rab11-family interacting protein 2en
dc.typeArticle (peer-reviewed)en
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