Acute LPS exposure enhances susceptibility to peripheral prion infection
Abstract After peripheral infections, the initial accumulation of prions within secondary lymphoid tissues is essential for the transmission of disease to the brain. Macrophages are considered to sequester or destroy prions, but little was known of their impact on disease susceptibility after a peri...
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Nature Portfolio
2025-03-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-94003-3 |
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| author | Reiss Pal Charlotte M. Thomas Khalid Salamat Stephen J. Jenkins Barry M. Bradford Neil A. Mabbott |
| author_facet | Reiss Pal Charlotte M. Thomas Khalid Salamat Stephen J. Jenkins Barry M. Bradford Neil A. Mabbott |
| author_sort | Reiss Pal |
| collection | DOAJ |
| description | Abstract After peripheral infections, the initial accumulation of prions within secondary lymphoid tissues is essential for the transmission of disease to the brain. Macrophages are considered to sequester or destroy prions, but little was known of their impact on disease susceptibility after a peripheral infection. Inflammation in the peritoneal cavity can trigger the macrophage disappearance reaction, whereby the macrophages are temporarily contained within cellular aggregates on the mesothelium. We studied the impact of the bacterial lipopolysaccharide (LPS)-mediated macrophage disappearance reaction on susceptibility to an intraperitoneal prion infection. Intraperitoneal LPS injection significantly enhanced prion disease susceptibility approximately 100X when given 24–3 h before infection. The effects on disease susceptibility coincided with the reduced abundance of macrophages within the peritoneal cavity at the time of infection and the enhanced early accumulation of prions in the spleen. This suggests that the reduced recoverable abundance of macrophages in the peritoneal cavity following acute LPS-treatment, increased disease susceptibility by enhancing the initial propagation of the prions from site of exposure (peritoneal cavity) to the spleen from where they subsequently spread to the brain. Further studies may help identify novel macrophage-targeted treatments that can reduce susceptibility to peripherally acquired prion infections. |
| format | Article |
| id | doaj-art-e9c9b31bd84c40a8856d02d7b46e105f |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-e9c9b31bd84c40a8856d02d7b46e105f2025-08-20T02:41:33ZengNature PortfolioScientific Reports2045-23222025-03-0115111510.1038/s41598-025-94003-3Acute LPS exposure enhances susceptibility to peripheral prion infectionReiss Pal0Charlotte M. Thomas1Khalid Salamat2Stephen J. Jenkins3Barry M. Bradford4Neil A. Mabbott5The Roslin Institute & Royal (Dick) School of Veterinary Studies, University of EdinburghThe Roslin Institute & Royal (Dick) School of Veterinary Studies, University of EdinburghThe Roslin Institute & Royal (Dick) School of Veterinary Studies, University of EdinburghQueens Medical Research Institute, University of Edinburgh Centre for Inflammation ResearchThe Roslin Institute & Royal (Dick) School of Veterinary Studies, University of EdinburghThe Roslin Institute & Royal (Dick) School of Veterinary Studies, University of EdinburghAbstract After peripheral infections, the initial accumulation of prions within secondary lymphoid tissues is essential for the transmission of disease to the brain. Macrophages are considered to sequester or destroy prions, but little was known of their impact on disease susceptibility after a peripheral infection. Inflammation in the peritoneal cavity can trigger the macrophage disappearance reaction, whereby the macrophages are temporarily contained within cellular aggregates on the mesothelium. We studied the impact of the bacterial lipopolysaccharide (LPS)-mediated macrophage disappearance reaction on susceptibility to an intraperitoneal prion infection. Intraperitoneal LPS injection significantly enhanced prion disease susceptibility approximately 100X when given 24–3 h before infection. The effects on disease susceptibility coincided with the reduced abundance of macrophages within the peritoneal cavity at the time of infection and the enhanced early accumulation of prions in the spleen. This suggests that the reduced recoverable abundance of macrophages in the peritoneal cavity following acute LPS-treatment, increased disease susceptibility by enhancing the initial propagation of the prions from site of exposure (peritoneal cavity) to the spleen from where they subsequently spread to the brain. Further studies may help identify novel macrophage-targeted treatments that can reduce susceptibility to peripherally acquired prion infections.https://doi.org/10.1038/s41598-025-94003-3Prion diseasesTransmissible spongiform encephalopathiesDisease susceptibilityMacrophageLPSSpleen |
| spellingShingle | Reiss Pal Charlotte M. Thomas Khalid Salamat Stephen J. Jenkins Barry M. Bradford Neil A. Mabbott Acute LPS exposure enhances susceptibility to peripheral prion infection Scientific Reports Prion diseases Transmissible spongiform encephalopathies Disease susceptibility Macrophage LPS Spleen |
| title | Acute LPS exposure enhances susceptibility to peripheral prion infection |
| title_full | Acute LPS exposure enhances susceptibility to peripheral prion infection |
| title_fullStr | Acute LPS exposure enhances susceptibility to peripheral prion infection |
| title_full_unstemmed | Acute LPS exposure enhances susceptibility to peripheral prion infection |
| title_short | Acute LPS exposure enhances susceptibility to peripheral prion infection |
| title_sort | acute lps exposure enhances susceptibility to peripheral prion infection |
| topic | Prion diseases Transmissible spongiform encephalopathies Disease susceptibility Macrophage LPS Spleen |
| url | https://doi.org/10.1038/s41598-025-94003-3 |
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