Increased lethality of respiratory infection by Streptococcus pneumoniae in the Dp16 mouse model of Down syndrome
Abstract Objectives We sought to investigate whether the Dp16 mouse model of Down syndrome (DS) is more susceptible to severe and lethal respiratory tract infection by Streptococcus pneumoniae. Study Design We infected controls and Dp16 mice with Streptococcus pneumoniae and measured survival rates....
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-12-01
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| Series: | FASEB BioAdvances |
| Online Access: | https://doi.org/10.1096/fba.2023-00091 |
| _version_ | 1797359533452951552 |
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| author | Kelley L. Colvin Robert J. Elliott Desiree M. Goodman Julie Harral Edward G. Barrett Michael E. Yeager |
| author_facet | Kelley L. Colvin Robert J. Elliott Desiree M. Goodman Julie Harral Edward G. Barrett Michael E. Yeager |
| author_sort | Kelley L. Colvin |
| collection | DOAJ |
| description | Abstract Objectives We sought to investigate whether the Dp16 mouse model of Down syndrome (DS) is more susceptible to severe and lethal respiratory tract infection by Streptococcus pneumoniae. Study Design We infected controls and Dp16 mice with Streptococcus pneumoniae and measured survival rates. We compared cytokine production by primary lung cell cultures exposed to Streptococcus pneumoniae. We examined lung protein expression for interferon signaling related pathways. We characterized the histopathology and quantified the extent of bronchus‐associated lymphoid tissue. Finally, we examined mouse tissues for the presence of oligomeric tau protein. Results We found that the Dp16 mouse model of DS displayed significantly higher susceptibility to lethal respiratory infection with Streptococcus pneumoniae compared to control mice. Lung cells cultured from Dp16 mice displayed unique secreted cytokine profiles compared to control mice. The Dp16 mouse lungs were characterized by profound lobar pneumonia with massive diffuse consolidation involving nearly the entire lobe. Marked red hepatization was noted, and Dp16 mice lungs contained numerous bronchus‐associated lymphoid tissues that were highly follicularized. Compared to uninfected mice, both control mice and Dp16 mice infected with Streptococcus pneumoniae showed evidence of oligomeric tau aggregates. Conclusions Increased susceptibility to severe respiratory tract infection with Streptococcus pneumoniae in Dp16 mice closely phenocopies infection in individuals with DS. The increase does not appear to be linked to overexpression of mouse interferon genes syntenic to human chromosome 21. |
| first_indexed | 2024-03-08T15:25:11Z |
| format | Article |
| id | doaj.art-123a846c4e7745399ebb91fbc07f2727 |
| institution | Directory Open Access Journal |
| issn | 2573-9832 |
| language | English |
| last_indexed | 2024-03-08T15:25:11Z |
| publishDate | 2023-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | FASEB BioAdvances |
| spelling | doaj.art-123a846c4e7745399ebb91fbc07f27272024-01-10T09:30:40ZengWileyFASEB BioAdvances2573-98322023-12-0151252854010.1096/fba.2023-00091Increased lethality of respiratory infection by Streptococcus pneumoniae in the Dp16 mouse model of Down syndromeKelley L. Colvin0Robert J. Elliott1Desiree M. Goodman2Julie Harral3Edward G. Barrett4Michael E. Yeager5Department of Bioengineering University of Colorado Aurora Colorado USADepartment of Bioengineering University of Colorado Aurora Colorado USALinda Crnic Institute for Down Syndrome, University of Colorado Aurora Colorado USAUniversity of Colorado Denver Health Sciences Aurora Colorado USALovelace Biomedical Research Institute Albuquerque New Mexico USADepartment of Bioengineering University of Colorado Aurora Colorado USAAbstract Objectives We sought to investigate whether the Dp16 mouse model of Down syndrome (DS) is more susceptible to severe and lethal respiratory tract infection by Streptococcus pneumoniae. Study Design We infected controls and Dp16 mice with Streptococcus pneumoniae and measured survival rates. We compared cytokine production by primary lung cell cultures exposed to Streptococcus pneumoniae. We examined lung protein expression for interferon signaling related pathways. We characterized the histopathology and quantified the extent of bronchus‐associated lymphoid tissue. Finally, we examined mouse tissues for the presence of oligomeric tau protein. Results We found that the Dp16 mouse model of DS displayed significantly higher susceptibility to lethal respiratory infection with Streptococcus pneumoniae compared to control mice. Lung cells cultured from Dp16 mice displayed unique secreted cytokine profiles compared to control mice. The Dp16 mouse lungs were characterized by profound lobar pneumonia with massive diffuse consolidation involving nearly the entire lobe. Marked red hepatization was noted, and Dp16 mice lungs contained numerous bronchus‐associated lymphoid tissues that were highly follicularized. Compared to uninfected mice, both control mice and Dp16 mice infected with Streptococcus pneumoniae showed evidence of oligomeric tau aggregates. Conclusions Increased susceptibility to severe respiratory tract infection with Streptococcus pneumoniae in Dp16 mice closely phenocopies infection in individuals with DS. The increase does not appear to be linked to overexpression of mouse interferon genes syntenic to human chromosome 21.https://doi.org/10.1096/fba.2023-00091 |
| spellingShingle | Kelley L. Colvin Robert J. Elliott Desiree M. Goodman Julie Harral Edward G. Barrett Michael E. Yeager Increased lethality of respiratory infection by Streptococcus pneumoniae in the Dp16 mouse model of Down syndrome FASEB BioAdvances |
| title | Increased lethality of respiratory infection by Streptococcus pneumoniae in the Dp16 mouse model of Down syndrome |
| title_full | Increased lethality of respiratory infection by Streptococcus pneumoniae in the Dp16 mouse model of Down syndrome |
| title_fullStr | Increased lethality of respiratory infection by Streptococcus pneumoniae in the Dp16 mouse model of Down syndrome |
| title_full_unstemmed | Increased lethality of respiratory infection by Streptococcus pneumoniae in the Dp16 mouse model of Down syndrome |
| title_short | Increased lethality of respiratory infection by Streptococcus pneumoniae in the Dp16 mouse model of Down syndrome |
| title_sort | increased lethality of respiratory infection by streptococcus pneumoniae in the dp16 mouse model of down syndrome |
| url | https://doi.org/10.1096/fba.2023-00091 |
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