{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T16:04:39Z","timestamp":1785945879774,"version":"3.56.0"},"reference-count":65,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,9,14]],"date-time":"2025-09-14T00:00:00Z","timestamp":1757808000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1017554"],"award-info":[{"award-number":["OPP1017554"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anim Models and Exp Med"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Bacterial pneumonia remains a leading cause of morbidity and mortality worldwide despite the widespread availability of antibiotics. Novel pneumonia therapies and biomarkers are urgently needed to improve outcomes and advance personalized therapy. Using an established baboon model of\n                      <jats:italic>S. pneumoniae<\/jats:italic>\n                      pneumonia, we sought to characterize the temporal dynamics of pneumonia host responses to identify novel potential diagnostic and therapeutic molecular targets.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed whole blood transcriptomics, unbiased proteomics, and peripheral cytokine measurements serially in baboons inoculated with\n                      <jats:italic>S. pneumoniae<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200923) or saline (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200910) and modeled the peripheral blood host response using principal components analysis and complex sparse logistic regression. Differentially expressed genes were analyzed for pathway analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Inoculated animals developed characteristic signs and symptoms of pneumonia. A 39\u2010gene signature was derived that classified\n                      <jats:italic>S. pneumoniae<\/jats:italic>\n                      infection with high accuracy (auROC 0.9 and 0.99 at 24 and 48\u2009h post\u2010inoculation, respectively). Similar performance was observed for 48\u2010h biomarker signatures derived from peripheral blood plasma proteomic and cytokine measurements (both auROC &gt;0.9). The gene signature retained strong diagnostic performance (auROC\u2009=\u20090.88) when transformed to human orthologs and applied to patients with acute respiratory illness (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200934) or healthy controls (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200920). Pathway analysis at 48\u2009h identified down\u2010regulation of mitophagy and glucocorticoid signaling in peripheral blood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      We report novel peripheral blood gene and protein expression signatures of\n                      <jats:italic>S. pneumoniae<\/jats:italic>\n                      pneumonia that could improve pneumonia diagnosis and found distinct pathways that may be amenable to modulation. Our findings illustrate how non\u2010human primate models of bacterial pneumonia can successfully translate biomarker discoveries to patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ame2.70079","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T06:24:45Z","timestamp":1757917485000},"page":"1896-1907","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Molecular dynamics of the host response to\n                    <i>Streptococcus pneumoniae<\/i>\n                    pneumonia in baboons"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6545-8803","authenticated-orcid":false,"given":"Bryan D.","family":"Kraft","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine Duke University School of Medicine  Durham North Carolina USA"},{"name":"Durham Veterans Affairs Health Care System  Durham North Carolina USA"},{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine Washington University School of Medicine  Saint Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashlee M.","family":"Valente","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Diagnostics and Innovation Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ephraim L.","family":"Tsalik","sequence":"additional","affiliation":[{"name":"Durham Veterans Affairs Health Care System  Durham North Carolina USA"},{"name":"Center for Infectious Disease Diagnostics and Innovation Duke University School of Medicine  Durham North Carolina USA"},{"name":"Division of Infectious Diseases, Department of Medicine Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micah T.","family":"McClain","sequence":"additional","affiliation":[{"name":"Durham Veterans Affairs Health Care System  Durham North Carolina USA"},{"name":"Center for Infectious Disease Diagnostics and Innovation Duke University School of Medicine  Durham North Carolina USA"},{"name":"Division of Infectious Diseases, Department of Medicine Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marshall","family":"Nichols","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Diagnostics and Innovation Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas W.","family":"Burke","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Diagnostics and Innovation Duke University School of Medicine  Durham North Carolina USA"},{"name":"Division of Infectious Diseases, Department of Medicine Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Henao","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Diagnostics and Innovation Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik J.","family":"Soderblom","sequence":"additional","affiliation":[{"name":"Proteomics and Metabolomics Shared Resource Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Will","family":"Thompson","sequence":"additional","affiliation":[{"name":"Proteomics and Metabolomics Shared Resource Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Arthur","family":"Moseley","sequence":"additional","affiliation":[{"name":"Proteomics and Metabolomics Shared Resource Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori L.","family":"Hudson","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Diagnostics and Innovation Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Veldman","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Diagnostics and Innovation Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga M.","family":"Better","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Diagnostics and Innovation Duke University School of Medicine  Durham North Carolina 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