The TLR4 adaptor TRAM controls the phagocytosis of Gram-negative bacteria by interacting with the Rab11-family interacting protein 2
dc.contributor.author | Skjesol, Astrid | |
dc.contributor.author | Yurchenko, Mariia | |
dc.contributor.author | Bösl, Korbinian | |
dc.contributor.author | Gravastrand, Caroline | |
dc.contributor.author | Nilsen, Kaja Elisabeth | |
dc.contributor.author | Grøvdal, Lene Melsæther | |
dc.contributor.author | Agliano, Federica | |
dc.contributor.author | Patane, Francesco | |
dc.contributor.author | Lentini, Germana | |
dc.contributor.author | Kim, Hera | |
dc.contributor.author | Teti, Giuseppe | |
dc.contributor.author | Kumar Sharma, Aditya | |
dc.contributor.author | Kandasamy, Richard K. | |
dc.contributor.author | Sporsheim, Bjørnar | |
dc.contributor.author | Starheim, Kristian K. | |
dc.contributor.author | Golenbock, Douglas T. | |
dc.contributor.author | Stenmark, Harald | |
dc.contributor.author | McCaffrey, Mary | |
dc.contributor.author | Espevik, Terje | |
dc.contributor.author | Husebye, Harald | |
dc.contributor.funder | Norges Teknisk-Naturvitenskapelige Universitet | en |
dc.contributor.funder | Norges Forskningsråd | en |
dc.contributor.funder | Liaison Committee for Education, Research and Innovation, Norway | en |
dc.date.accessioned | 2019-11-19T11:59:27Z | |
dc.date.available | 2019-11-19T11:59:27Z | |
dc.date.issued | 2019-03-18 | |
dc.description.abstract | Author 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.sponsorship | 46082500; 80420223; 223255/F50; FRIMEDBIO program (275876); 50052400 | en |
dc.description.status | Peer reviewed | en |
dc.description.version | Published Version | en |
dc.format.mimetype | application/pdf | en |
dc.identifier.articleid | e1007684 | en |
dc.identifier.citation | Skjesol, 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.1007684 | en |
dc.identifier.doi | 10.1371/journal.ppat.1007684 | en |
dc.identifier.eissn | 1553-7374 | |
dc.identifier.endpage | 30 | en |
dc.identifier.issn | 1553-7366 | |
dc.identifier.issued | 3 | en |
dc.identifier.journaltitle | PLoS Pathogens | en |
dc.identifier.startpage | 1 | en |
dc.identifier.uri | https://hdl.handle.net/10468/9067 | |
dc.identifier.volume | 15 | en |
dc.language.iso | en | en |
dc.publisher | PLoS | en |
dc.relation.uri | https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007684 | |
dc.rights | © 2019 Skjesol et al | en |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en |
dc.subject | Phagocytosis | en |
dc.subject | Toll-like receptor 4 (TLR4) | en |
dc.subject | Rab11 family interacting protein 2 (FIP2) | en |
dc.title | The TLR4 adaptor TRAM controls the phagocytosis of Gram-negative bacteria by interacting with the Rab11-family interacting protein 2 | en |
dc.type | Article (peer-reviewed) | en |
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