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Liver sinusoidal cells eliminate blood-borne phage K1F
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Sánchez Romano, Javier, Simón-Santamaria, Jaione, McCourt, Peter, Smedsrød, Bård, Erlend Mortensen, Kim, Sagona, Antonia P., Sørensen, Karen Kristine and Larsen, Anett Kristin (2024) Liver sinusoidal cells eliminate blood-borne phage K1F. mSphere, 9 (3). e0070223. doi:10.1128/msphere.00702-23 ISSN 2379-5042. (In Press)
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WRAP-Liver-sinusoidal-cells-eliminate-blood-borne-phage-K1F-2024.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (2380Kb) | Preview |
Official URL: https://doi.org/10.1128/msphere.00702-23
Abstract
Phage 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 (K1Fgfp) in mice. Circulatory half-life, organ, and hepatocellular distribution of K1Fgfp 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 K1Fgfp load was eliminated from the blood within 20 min, and 94% of the total retrieved K1Fgfp 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 K1Fgfp corroborated inactivation following endocytosis. This study is the first to identify phage distribution in the liver at the hepatocellular level, confirming clearance of K1Fgfp performed mostly by KCs with a significant uptake also in LSECs.
Item Type: | Journal Article | ||||||||||||
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Alternative Title: | |||||||||||||
Subjects: | Q Science > QR Microbiology | ||||||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||||||
Library of Congress Subject Headings (LCSH): | Bacteriophages -- Therapeutic use, Endothelial cells, Liver cells | ||||||||||||
Journal or Publication Title: | mSphere | ||||||||||||
Publisher: | American Society for Microbiology | ||||||||||||
ISSN: | 2379-5042 | ||||||||||||
Official Date: | March 2024 | ||||||||||||
Dates: |
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Volume: | 9 | ||||||||||||
Number: | 3 | ||||||||||||
Article Number: | e0070223 | ||||||||||||
DOI: | 10.1128/msphere.00702-23 | ||||||||||||
Status: | Peer Reviewed | ||||||||||||
Publication Status: | In Press | ||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||
Date of first compliant deposit: | 29 February 2024 | ||||||||||||
Date of first compliant Open Access: | 29 February 2024 | ||||||||||||
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