{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T18:42:28Z","timestamp":1760553748349,"version":"build-2065373602"},"reference-count":46,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T00:00:00Z","timestamp":1698624000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FASEB BioAdvances"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>We sought to investigate whether the Dp16 mouse model of Down syndrome (DS) is more susceptible to severe and lethal respiratory tract infection by <jats:italic>Streptococcus pneumoniae<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>We infected controls and Dp16 mice with <jats:italic>Streptococcus pneumoniae<\/jats:italic> and measured survival rates. We compared cytokine production by primary lung cell cultures exposed to <jats:italic>Streptococcus pneumoniae<\/jats:italic>. We examined lung protein expression for interferon signaling related pathways. We characterized the histopathology and quantified the extent of bronchus\u2010associated lymphoid tissue. Finally, we examined mouse tissues for the presence of oligomeric tau protein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that the Dp16 mouse model of DS displayed significantly higher susceptibility to lethal respiratory infection with <jats:italic>Streptococcus pneumoniae<\/jats:italic> 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\u2010associated lymphoid tissues that were highly follicularized. Compared to uninfected mice, both control mice and Dp16 mice infected with <jats:italic>Streptococcus pneumoniae<\/jats:italic> showed evidence of oligomeric tau aggregates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Increased susceptibility to severe respiratory tract infection with <jats:italic>Streptococcus pneumoniae<\/jats:italic> 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.<\/jats:p><\/jats:sec>","DOI":"10.1096\/fba.2023-00091","type":"journal-article","created":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T07:51:29Z","timestamp":1698652289000},"page":"528-540","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Increased lethality of respiratory infection by <i>Streptococcus pneumoniae<\/i> in the Dp16 mouse model of Down syndrome"],"prefix":"10.1096","volume":"5","author":[{"given":"Kelley L.","family":"Colvin","sequence":"first","affiliation":[{"name":"Department of Bioengineering University of Colorado  Aurora Colorado USA"},{"name":"Linda Crnic Institute for Down Syndrome, University of Colorado  Aurora Colorado USA"},{"name":"University of Colorado Denver Health Sciences  Aurora Colorado 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