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dc.contributor.authorRomano, Javier Sánchez
dc.contributor.authorSimon-Santamaria, Jaione
dc.contributor.authorMcCourt, Peter Anthony
dc.contributor.authorSmedsrød, Bård Helge
dc.contributor.authorMortensen, Kim Erlend
dc.contributor.authorSagona, Antonia
dc.contributor.authorSørensen, Karen Kristine
dc.contributor.authorLarsen, Anett Kristin
dc.date.accessioned2024-09-13T11:08:12Z
dc.date.available2024-09-13T11:08:12Z
dc.date.issued2024-02-28
dc.description.abstractPhage treatment has regained attention due to an increase in multiresistant bacteria. For phage therapy to be successful, phages must reach their target bacteria in sufficiently high numbers. Blood-borne phages are believed to be captured by macrophages in the liver and spleen. Since liver sinusoids also consist of specialized scavenger liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs), this study investigated the contribution of both cell types in the elimination of Escherichia coli phage K1Fg10b::gfp (K1F<sup>gfp</sup>) in mice. Circulatory half-life, organ, and hepatocellular distribution of K1F<sup>gfp</sup> were determined following intravenous administration. Internalization of K1Fgfp and effects of phage opsonization on uptake were explored using primary mouse and human LSEC and KC cultures. When inoculated with 107 virions, >95% of the total K1F<sup>gfp</sup> load was eliminated from the blood within 20 min, and 94% of the total retrieved K1F<sup>gfp</sup> was localized to the liver. Higher doses resulted in slower elimination, possibly reflecting temporary saturation of liver scavenging capacity. Phage DNA was detected in both cell types, with a KC:LSEC ratio of 12:1 per population following cell isolation. Opsonization with plasma proteins increased time-dependent cellular uptake in both LSECs and KCs in vitro. Internalized phages were rapidly transported along the endocytic pathway to lysosomal compartments. Reduced viability of intracellular K1F<sup>gfp</sup> corroborated inactivation following endocytosis. This study is the first to identify phage distribution in the liver at the hepatocellular level, confirming clearance of K1F<sup>gfp</sup> performed mostly by KCs with a significant uptake also in LSECs.en_US
dc.identifier.citationRomano, Simon-Santamaria, McCourt, Smedsrød, Mortensen, Sagona, Sørensen, Larsen. Liver sinusoidal cells eliminate blood-borne phage K1F. mSphere. 2024;9(3)en_US
dc.identifier.cristinIDFRIDAID 2263257
dc.identifier.doi10.1128/msphere.00702-23
dc.identifier.issn2379-5042
dc.identifier.urihttps://hdl.handle.net/10037/34711
dc.language.isoengen_US
dc.publisherAmerican Society for Microbiologyen_US
dc.relation.journalmSphere
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2024 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.titleLiver sinusoidal cells eliminate blood-borne phage K1Fen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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Attribution 4.0 International (CC BY 4.0)
Med mindre det står noe annet, er denne innførselens lisens beskrevet som Attribution 4.0 International (CC BY 4.0)